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Erschienen in: Discover Oncology 5/2018

09.07.2018 | Review

RAGE and Its Ligands: Molecular Interplay Between Glycation, Inflammation, and Hallmarks of Cancer—a Review

verfasst von: Gowri Palanissami, Solomon F. D. Paul

Erschienen in: Discover Oncology | Ausgabe 5/2018

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Abstract

Risk of cancer especially of colon, breast, and pancreas is high in diabetic and obese patients, with potential involvement of augmented expression of RAGE (receptor for advanced glycation end products) and its ligands, namely AGEs (advanced glycation end products), HMGB1 (high-mobility group box 1 protein), and S100 group of proteins. Studies have reported the involvement of RAGE activation by its ligands in growth and survival of cancers, including metastasis and poor prognosis. We propose that this receptor-ligand axis provides the molecular link between certain pre-existing states as hypoxia, hyperglycemia, glycation, inflammation, oxidative stress, and onset of cancers. The chronic inflammatory, hyperglycemic milieu accompanied by glycoxidative stress as in diabetes and obesity, concomitant with the formation of RAGE ligands, instigates RAGE and cancer stem cells, leading to the oncogenic transformation of normal and pre-malignant tissues towards development of neoplasms. We have aimed to elucidate the complete signalling map initiated upon RAGE-ligand splicing, from oncogenesis to progression, epithelial-mesenchymal transition, invasion, cancer stem cell renewal, chemo-resistance, and cancer relapse. We have attributed the complex molecular functions of RAGE-ligand signalling cues to every aspect of cancer promotion, explaining the central network in bridging glycation, inflammation, oxidation, and the hallmarks of cancer. Underlining the substantial requisite for anti-neoplastic agents targeting RAGE and its ligands, we have explicitly discoursed RAGE and its allied components (AGEs, soluble RAGE, RAGE gene polymorphisms) as potential diagnostic and prognostic biomarkers for prompt detection of cancers and implication in impending RAGE-ligand directed, novel combinatorial, and targeted onco-therapeutics.
Literatur
1.
Zurück zum Zitat World Health Organization. Breast cancer estimated incidence, mortality and prevalence worldwide in 2012. 2012. URL: http://globocan iarc fr/old/FactSheets/cancers/breast-new asp [WebCite Cache ID 6aKrqTle9] World Health Organization. Breast cancer estimated incidence, mortality and prevalence worldwide in 2012. 2012. URL: http://​globocan iarc fr/old/FactSheets/cancers/breast-new asp [WebCite Cache ID 6aKrqTle9]
2.
Zurück zum Zitat Mathupala SP, Ko YH, Pedersen PL (2010) The pivotal roles of mitochondria in cancer: Warburg and beyond and encouraging prospects for effective therapies. BBA-Bioenergetics 1797(6):1225–1230PubMedCrossRef Mathupala SP, Ko YH, Pedersen PL (2010) The pivotal roles of mitochondria in cancer: Warburg and beyond and encouraging prospects for effective therapies. BBA-Bioenergetics 1797(6):1225–1230PubMedCrossRef
5.
Zurück zum Zitat Turner DP (2015) Advanced glycation end-products: a biological consequence of lifestyle contributing to cancer disparity. Cancer Res 75(10):1925–1929PubMedPubMedCentralCrossRef Turner DP (2015) Advanced glycation end-products: a biological consequence of lifestyle contributing to cancer disparity. Cancer Res 75(10):1925–1929PubMedPubMedCentralCrossRef
6.
Zurück zum Zitat Heijst JWJ, Niessen HWM, Hoekman K, Schalkwijk CG (2005) Advanced glycation end products in human cancer tissues: detection of Nε-(carboxymethyl) lysine and argpyrimidine. Ann N Y Acad Sci 1043(1):725–733PubMedCrossRef Heijst JWJ, Niessen HWM, Hoekman K, Schalkwijk CG (2005) Advanced glycation end products in human cancer tissues: detection of Nε-(carboxymethyl) lysine and argpyrimidine. Ann N Y Acad Sci 1043(1):725–733PubMedCrossRef
7.
Zurück zum Zitat Ashraf JM, Shahab U, Tabrez S, Lee EJ, Choi I, Yusuf MA, Ahmad S (2016) DNA glycation from 3-deoxyglucosone leads to the formation of AGEs: potential role in cancer auto-antibodies. Cell Biochem Biophys 74(1):67–77PubMedCrossRef Ashraf JM, Shahab U, Tabrez S, Lee EJ, Choi I, Yusuf MA, Ahmad S (2016) DNA glycation from 3-deoxyglucosone leads to the formation of AGEs: potential role in cancer auto-antibodies. Cell Biochem Biophys 74(1):67–77PubMedCrossRef
8.
Zurück zum Zitat Synold T, Xi B, Wuenschell GE, Tamae D, Figarola JL, Rahbar S, Termini J (2008) Advanced glycation end products of DNA: quantification of N 2-(1-carboxyethyl)-2′-deoxyguanosine in biological samples by liquid chromatography electrospray ionization tandem mass spectrometry. Chem Res Toxicol 21(11):2148–2155PubMedPubMedCentralCrossRef Synold T, Xi B, Wuenschell GE, Tamae D, Figarola JL, Rahbar S, Termini J (2008) Advanced glycation end products of DNA: quantification of N 2-(1-carboxyethyl)-2′-deoxyguanosine in biological samples by liquid chromatography electrospray ionization tandem mass spectrometry. Chem Res Toxicol 21(11):2148–2155PubMedPubMedCentralCrossRef
9.
Zurück zum Zitat Yamagishi S, Matsui T, Fukami K (2015) Role of receptor for advanced glycation end products (RAGE) and its ligands in cancer risk. Rejuvenation Res 18(1):48–56PubMedCrossRef Yamagishi S, Matsui T, Fukami K (2015) Role of receptor for advanced glycation end products (RAGE) and its ligands in cancer risk. Rejuvenation Res 18(1):48–56PubMedCrossRef
10.
Zurück zum Zitat Logsdon CD, Fuentes MK, Huang EH, Arumugam T (2007) RAGE and RAGE ligands in cancer. Curr Mol Med 7(8):777–789PubMedCrossRef Logsdon CD, Fuentes MK, Huang EH, Arumugam T (2007) RAGE and RAGE ligands in cancer. Curr Mol Med 7(8):777–789PubMedCrossRef
13.
Zurück zum Zitat Wei Y, Chen L, Chen J, Ge L, He RQ (2009) Rapid glycation with D-ribose induces globular amyloid-like aggregations of BSA with high cytotoxicity to SH-SY5Y cells. BMC Cell Biol 10(1):10PubMedPubMedCentralCrossRef Wei Y, Chen L, Chen J, Ge L, He RQ (2009) Rapid glycation with D-ribose induces globular amyloid-like aggregations of BSA with high cytotoxicity to SH-SY5Y cells. BMC Cell Biol 10(1):10PubMedPubMedCentralCrossRef
14.
Zurück zum Zitat Baraka-Vidot J, Guerin-Dubourg A, Bourdon E, Rondeau P (2012) Impaired drug-binding capacities of in vitro and in vivo glycated albumin. Biochimie 94(9):1960–1967PubMedCrossRef Baraka-Vidot J, Guerin-Dubourg A, Bourdon E, Rondeau P (2012) Impaired drug-binding capacities of in vitro and in vivo glycated albumin. Biochimie 94(9):1960–1967PubMedCrossRef
15.
Zurück zum Zitat Ansari NA, Ali R (2011) Physicochemical analysis of poly-L-lysine: an insight into the changes induced in lysine residues of proteins on modification with glucose. IUBMB Life 63(1):26–29PubMedCrossRef Ansari NA, Ali R (2011) Physicochemical analysis of poly-L-lysine: an insight into the changes induced in lysine residues of proteins on modification with glucose. IUBMB Life 63(1):26–29PubMedCrossRef
16.
Zurück zum Zitat Bao J-M, He M-Y, Liu Y-W, Lu Y-J, Hong Y-Q, Luo H-H, Ren Z-L, Zhao S-C, Jiang Y (2015) AGE/RAGE/Akt pathway contributes to prostate cancer cell proliferation by promoting Rb phosphorylation and degradation. Am J Cancer Res 5(5):1741PubMedPubMedCentral Bao J-M, He M-Y, Liu Y-W, Lu Y-J, Hong Y-Q, Luo H-H, Ren Z-L, Zhao S-C, Jiang Y (2015) AGE/RAGE/Akt pathway contributes to prostate cancer cell proliferation by promoting Rb phosphorylation and degradation. Am J Cancer Res 5(5):1741PubMedPubMedCentral
17.
Zurück zum Zitat Yaser AM, Huang Y, Zhou RR, Hu GS, Xiao MF, Huang ZB, Duan CJ, Tian W, Tang DL, Fan XG (2012) The role of receptor for advanced glycation end products (RAGE) in the proliferation of hepatocellular carcinoma. Int J Mol Sci 13(5):5982–5997PubMedPubMedCentralCrossRef Yaser AM, Huang Y, Zhou RR, Hu GS, Xiao MF, Huang ZB, Duan CJ, Tian W, Tang DL, Fan XG (2012) The role of receptor for advanced glycation end products (RAGE) in the proliferation of hepatocellular carcinoma. Int J Mol Sci 13(5):5982–5997PubMedPubMedCentralCrossRef
18.
Zurück zum Zitat Matou-Nasri S, Sharaf H, Wang Q, Almobadel N, Rabhan Z, Al-Eidi H, Yahya WB, Trivilegio T, Ali R, Al-Shanti N, Ahmed N (2017) Biological impact of advanced glycation endproducts on estrogen receptor-positive MCF-7 breast cancer cells. Biochim Biophys Acta (BBA) Mol Basis Dis 1863(11):2808–2820CrossRef Matou-Nasri S, Sharaf H, Wang Q, Almobadel N, Rabhan Z, Al-Eidi H, Yahya WB, Trivilegio T, Ali R, Al-Shanti N, Ahmed N (2017) Biological impact of advanced glycation endproducts on estrogen receptor-positive MCF-7 breast cancer cells. Biochim Biophys Acta (BBA) Mol Basis Dis 1863(11):2808–2820CrossRef
19.
Zurück zum Zitat Fritz G (2011) RAGE: a single receptor fits multiple ligands. Trends Biochem Sci 36(12):625–632PubMedCrossRef Fritz G (2011) RAGE: a single receptor fits multiple ligands. Trends Biochem Sci 36(12):625–632PubMedCrossRef
20.
Zurück zum Zitat Xue J, Rai V, Singer D, Chabierski S, Xie J, Reverdatto S, Burz David S, Schmidt AM, Hoffmann R, Shekhtman A (2011) Advanced glycation end product recognition by the receptor for AGEs. Structure 19(5):722–732PubMedPubMedCentralCrossRef Xue J, Rai V, Singer D, Chabierski S, Xie J, Reverdatto S, Burz David S, Schmidt AM, Hoffmann R, Shekhtman A (2011) Advanced glycation end product recognition by the receptor for AGEs. Structure 19(5):722–732PubMedPubMedCentralCrossRef
21.
Zurück zum Zitat Cai W, Ramdas M, Zhu L, Chen X, Striker GE, Vlassara H (2012) Oral advanced glycation endproducts (AGEs) promote insulin resistance and diabetes by depleting the antioxidant defenses AGE receptor-1 and sirtuin 1. Proc Natl Acad Sci 109(39):15888–15893PubMedCrossRefPubMedCentral Cai W, Ramdas M, Zhu L, Chen X, Striker GE, Vlassara H (2012) Oral advanced glycation endproducts (AGEs) promote insulin resistance and diabetes by depleting the antioxidant defenses AGE receptor-1 and sirtuin 1. Proc Natl Acad Sci 109(39):15888–15893PubMedCrossRefPubMedCentral
22.
Zurück zum Zitat Nedić O, Rattan SIS, Grune T, Trougakos IP (2013) Molecular effects of advanced glycation end products on cell signalling pathways, ageing and pathophysiology. Free Radic Res 47(sup1):28–38PubMedCrossRef Nedić O, Rattan SIS, Grune T, Trougakos IP (2013) Molecular effects of advanced glycation end products on cell signalling pathways, ageing and pathophysiology. Free Radic Res 47(sup1):28–38PubMedCrossRef
23.
Zurück zum Zitat Ramasamy R, Vannucci SJ, Yan SS, Herold K, Yan SF, Schmidt AM (2005) Advanced glycation end products and RAGE: a common thread in aging, diabetes, neurodegeneration, and inflammation. Glycobiology 15(7):16R–28RPubMedCrossRef Ramasamy R, Vannucci SJ, Yan SS, Herold K, Yan SF, Schmidt AM (2005) Advanced glycation end products and RAGE: a common thread in aging, diabetes, neurodegeneration, and inflammation. Glycobiology 15(7):16R–28RPubMedCrossRef
24.
Zurück zum Zitat Srikanth V, Maczurek A, Phan T, Steele M, Westcott B, Juskiw D, Münch G (2011) Advanced glycation endproducts and their receptor RAGE in Alzheimer’s disease. Neurobiol Aging 32(5):763–777PubMedCrossRef Srikanth V, Maczurek A, Phan T, Steele M, Westcott B, Juskiw D, Münch G (2011) Advanced glycation endproducts and their receptor RAGE in Alzheimer’s disease. Neurobiol Aging 32(5):763–777PubMedCrossRef
25.
Zurück zum Zitat Diamanti-Kandarakis E, Piperi C, Patsouris E, Korkolopoulou P, Panidis D, Pawelczyk L, Papavassiliou AG, Duleba AJ (2007) Immunohistochemical localization of advanced glycation end-products (AGEs) and their receptor (RAGE) in polycystic and normal ovaries. Histochem Cell Biol 127(6):581–589PubMedCrossRef Diamanti-Kandarakis E, Piperi C, Patsouris E, Korkolopoulou P, Panidis D, Pawelczyk L, Papavassiliou AG, Duleba AJ (2007) Immunohistochemical localization of advanced glycation end-products (AGEs) and their receptor (RAGE) in polycystic and normal ovaries. Histochem Cell Biol 127(6):581–589PubMedCrossRef
26.
Zurück zum Zitat Gomes R, Silva MS, Quintas A, Cordeiro C, Freire A, Pereira P, Martins A, Monteiro E, Barroso E, Freire AP (2005) Argpyrimidine, a methylglyoxal-derived advanced glycation end-product in familial amyloidotic polyneuropathy. Biochem J 385(2):339–345PubMedPubMedCentralCrossRef Gomes R, Silva MS, Quintas A, Cordeiro C, Freire A, Pereira P, Martins A, Monteiro E, Barroso E, Freire AP (2005) Argpyrimidine, a methylglyoxal-derived advanced glycation end-product in familial amyloidotic polyneuropathy. Biochem J 385(2):339–345PubMedPubMedCentralCrossRef
28.
Zurück zum Zitat Ko S-Y, Ko H-A, Shieh T-M, Chang W-C, Chen H-I, Chang S-S, Lin I-H (2014) Cell migration is regulated by AGE-RAGE interaction in human oral cancer cells in vitro. PLoS One 9(10):e110542PubMedPubMedCentralCrossRef Ko S-Y, Ko H-A, Shieh T-M, Chang W-C, Chen H-I, Chang S-S, Lin I-H (2014) Cell migration is regulated by AGE-RAGE interaction in human oral cancer cells in vitro. PLoS One 9(10):e110542PubMedPubMedCentralCrossRef
29.
Zurück zum Zitat Nasser MW, Wani NA, Ahirwar DK, Powell CA, Ravi J, Elbaz M, Zhao H, Padilla L, Zhang X, Shilo K (2015) RAGE mediates S100A7-induced breast cancer growth and metastasis by modulating the tumor microenvironment. Cancer Res 75(6):974–985PubMedPubMedCentralCrossRef Nasser MW, Wani NA, Ahirwar DK, Powell CA, Ravi J, Elbaz M, Zhao H, Padilla L, Zhang X, Shilo K (2015) RAGE mediates S100A7-induced breast cancer growth and metastasis by modulating the tumor microenvironment. Cancer Res 75(6):974–985PubMedPubMedCentralCrossRef
30.
Zurück zum Zitat Kang R, Hou W, Zhang Q, Chen R, Lee YJ, Bartlett DL, Lotze MT, Tang D, Zeh HJ (2014) RAGE is essential for oncogenic KRAS-mediated hypoxic signaling in pancreatic cancer. Cell Death Dis 5(10):e1480PubMedPubMedCentralCrossRef Kang R, Hou W, Zhang Q, Chen R, Lee YJ, Bartlett DL, Lotze MT, Tang D, Zeh HJ (2014) RAGE is essential for oncogenic KRAS-mediated hypoxic signaling in pancreatic cancer. Cell Death Dis 5(10):e1480PubMedPubMedCentralCrossRef
31.
Zurück zum Zitat Hiba Z, Borden Katherine LB (2013) Mechanisms and insights into drug resistance in cancer. Front Pharmacol 4 Hiba Z, Borden Katherine LB (2013) Mechanisms and insights into drug resistance in cancer. Front Pharmacol 4
32.
Zurück zum Zitat Housman G, Byler S, Heerboth S, Lapinska K, Longacre M, Snyder N, Sarkar S (2014) Drug resistance in cancer: an overview. Cancers 6(3):1769–1792PubMedPubMedCentralCrossRef Housman G, Byler S, Heerboth S, Lapinska K, Longacre M, Snyder N, Sarkar S (2014) Drug resistance in cancer: an overview. Cancers 6(3):1769–1792PubMedPubMedCentralCrossRef
33.
Zurück zum Zitat Shi W, Jiang T, Nuciforo P, Hatzis C, Holmes E, Harbeck N, Sotiriou C, Peña L, Loi S, Rosa DD (2017) Pathway level alterations rather than mutations in single genes predict response to HER2-targeted therapies in the neo-ALTTO trial. Ann Oncol 28(1):128–135PubMed Shi W, Jiang T, Nuciforo P, Hatzis C, Holmes E, Harbeck N, Sotiriou C, Peña L, Loi S, Rosa DD (2017) Pathway level alterations rather than mutations in single genes predict response to HER2-targeted therapies in the neo-ALTTO trial. Ann Oncol 28(1):128–135PubMed
34.
Zurück zum Zitat Sullivan Lucas B, Gui Dan Y, Vander Heiden Matthew G (2016) Altered metabolite levels in cancer: implications for tumour biology and cancer therapy. Nat Rev Cancer 16(11):680–693PubMedCrossRef Sullivan Lucas B, Gui Dan Y, Vander Heiden Matthew G (2016) Altered metabolite levels in cancer: implications for tumour biology and cancer therapy. Nat Rev Cancer 16(11):680–693PubMedCrossRef
35.
Zurück zum Zitat Pelicano H, Dai J, Liu J, Pusztai L, Hammoudi N, Huang P, Xu R-H, Zhang W (2014) Mitochondrial dysfunction in some triple-negative breast cancer cell lines: role of mTOR pathway and therapeutic potential. Breast Cancer Res 16(5):434PubMedPubMedCentralCrossRef Pelicano H, Dai J, Liu J, Pusztai L, Hammoudi N, Huang P, Xu R-H, Zhang W (2014) Mitochondrial dysfunction in some triple-negative breast cancer cell lines: role of mTOR pathway and therapeutic potential. Breast Cancer Res 16(5):434PubMedPubMedCentralCrossRef
36.
Zurück zum Zitat Fais S, Venturi G, Gatenby B (2014) Microenvironmental acidosis in carcinogenesis and metastases: new strategies in prevention and therapy. Cancer Metastasis Rev 33(4):1095–1108PubMedPubMedCentralCrossRef Fais S, Venturi G, Gatenby B (2014) Microenvironmental acidosis in carcinogenesis and metastases: new strategies in prevention and therapy. Cancer Metastasis Rev 33(4):1095–1108PubMedPubMedCentralCrossRef
37.
Zurück zum Zitat Kellenberger LD, Bruin JE, Greenaway J, Campbell NE, Moorehead RA, Holloway AC, Petrik J (2010) The role of dysregulated glucose metabolism in epithelial ovarian cancer. J Oncol:2010 Kellenberger LD, Bruin JE, Greenaway J, Campbell NE, Moorehead RA, Holloway AC, Petrik J (2010) The role of dysregulated glucose metabolism in epithelial ovarian cancer. J Oncol:2010
39.
Zurück zum Zitat Gatenby Robert A, Gawlinski Edward T (2003) The glycolytic phenotype in carcinogenesis and tumor invasion. Cancer Res 63(14):3847–3854PubMed Gatenby Robert A, Gawlinski Edward T (2003) The glycolytic phenotype in carcinogenesis and tumor invasion. Cancer Res 63(14):3847–3854PubMed
40.
Zurück zum Zitat Ansari NA, Rasheed Z (2009) Non-enzymatic glycation of proteins: from diabetes to cancer. Biochem (Mosc) Suppl Ser B Biomed Chem 3(4):335–342 Ansari NA, Rasheed Z (2009) Non-enzymatic glycation of proteins: from diabetes to cancer. Biochem (Mosc) Suppl Ser B Biomed Chem 3(4):335–342
41.
Zurück zum Zitat Poulsen MW, Hedegaard RV, Andersen JM, de Courten B, Bügel S, Nielsen J, Skibsted LH, Dragsted LO (2013) Advanced glycation endproducts in food and their effects on health. Food Chem Toxicol 60:10–37PubMedCrossRef Poulsen MW, Hedegaard RV, Andersen JM, de Courten B, Bügel S, Nielsen J, Skibsted LH, Dragsted LO (2013) Advanced glycation endproducts in food and their effects on health. Food Chem Toxicol 60:10–37PubMedCrossRef
42.
Zurück zum Zitat Claudia L-C, Karen C-N (2010) Dietary advanced glycation end products and aging. Nutrients 2(12):1247–1265CrossRef Claudia L-C, Karen C-N (2010) Dietary advanced glycation end products and aging. Nutrients 2(12):1247–1265CrossRef
43.
Zurück zum Zitat Dion F, Laura S, Walter Katherine R, Nogueira Lourdes M, Hleb F, Turner Ryan Y, Mahtabuddin A, Salley Judith D, Ford Marvella E, Findlay VJ (2014) AGE metabolites: a biomarker linked to cancer disparity? Cancer Epidemiol Biomarkers Prev 23(10):2186–2191 Dion F, Laura S, Walter Katherine R, Nogueira Lourdes M, Hleb F, Turner Ryan Y, Mahtabuddin A, Salley Judith D, Ford Marvella E, Findlay VJ (2014) AGE metabolites: a biomarker linked to cancer disparity? Cancer Epidemiol Biomarkers Prev 23(10):2186–2191
44.
Zurück zum Zitat Junjeong C, Do Hee K, Hee JW, Seung KJ (2013) Metabolic interaction between cancer cells and stromal cells according to breast cancer molecular subtype. Breast Cancer Res 15(5):R78CrossRef Junjeong C, Do Hee K, Hee JW, Seung KJ (2013) Metabolic interaction between cancer cells and stromal cells according to breast cancer molecular subtype. Breast Cancer Res 15(5):R78CrossRef
45.
46.
Zurück zum Zitat Da W, Tingting L, Gengtai Y, Zhiyong S, Yanfeng H, Tingyu M, Jiang Y, Sihao L, Hao L, Guoxin L (2015) Overexpression of the receptor for advanced glycation endproducts (RAGE) is associated with poor prognosis in gastric cancer. PLoS One 10(4):e0122697CrossRef Da W, Tingting L, Gengtai Y, Zhiyong S, Yanfeng H, Tingyu M, Jiang Y, Sihao L, Hao L, Guoxin L (2015) Overexpression of the receptor for advanced glycation endproducts (RAGE) is associated with poor prognosis in gastric cancer. PLoS One 10(4):e0122697CrossRef
47.
Zurück zum Zitat Selvia S, Tarek A, Amr A (2017) Differentiation of RAGE expression in primary tumors and lymph node metastatic deposits of breast carcinoma. Imp J Interdiscip Res 3(6) Selvia S, Tarek A, Amr A (2017) Differentiation of RAGE expression in primary tumors and lymph node metastatic deposits of breast carcinoma. Imp J Interdiscip Res 3(6)
48.
Zurück zum Zitat Korwar Arvind M, Bhonsle Hemangi S, Chougale Ashok D, Kote Sachin S, Gawai Kachru R, Ghole Vikram S, Koppikar Chaitanyananda B, Kulkarni Mahesh J (2012) Analysis of AGE modified proteins and RAGE expression in HER2/neu negative invasive ductal carcinoma. Biochem Biophys Res Commun 419(3):490–494PubMedCrossRef Korwar Arvind M, Bhonsle Hemangi S, Chougale Ashok D, Kote Sachin S, Gawai Kachru R, Ghole Vikram S, Koppikar Chaitanyananda B, Kulkarni Mahesh J (2012) Analysis of AGE modified proteins and RAGE expression in HER2/neu negative invasive ductal carcinoma. Biochem Biophys Res Commun 419(3):490–494PubMedCrossRef
49.
Zurück zum Zitat Bing P, Hui R, Yijing M, Donghui L, Baoqi Y, Liang J, Ling P, Jing L, Liangui Y, Xiaofeng L (2012) High-density lipoprotein of patients with type 2 diabetes mellitus elevates the capability of promoting migration and invasion of breast cancer cells. Int J Cancer 131(1):70–82CrossRef Bing P, Hui R, Yijing M, Donghui L, Baoqi Y, Liang J, Ling P, Jing L, Liangui Y, Xiaofeng L (2012) High-density lipoprotein of patients with type 2 diabetes mellitus elevates the capability of promoting migration and invasion of breast cancer cells. Int J Cancer 131(1):70–82CrossRef
50.
Zurück zum Zitat Jin PL, Lin L, Qi Z, Yan ZR, Feng SW, Ying S (2012) Increased blood glycohemoglobin A1c levels lead to overestimation of arterial oxygen saturation by pulse oximetry in patients with type 2 diabetes. Cardiovasc Diabetol 11(1):110CrossRef Jin PL, Lin L, Qi Z, Yan ZR, Feng SW, Ying S (2012) Increased blood glycohemoglobin A1c levels lead to overestimation of arterial oxygen saturation by pulse oximetry in patients with type 2 diabetes. Cardiovasc Diabetol 11(1):110CrossRef
51.
Zurück zum Zitat Philippe R, Emmanuel B (2011) The glycation of albumin: structural and functional impacts. Biochimie 93(4):645–658CrossRef Philippe R, Emmanuel B (2011) The glycation of albumin: structural and functional impacts. Biochimie 93(4):645–658CrossRef
52.
Zurück zum Zitat Rouf MA, Safia H, Farzana K, Khursheed A, Asif A (2015) Structural changes in histone H2A by methylglyoxal generate highly immunogenic amorphous aggregates with implications in auto-immune response in cancer. Glycobiology 26(2):129–141 Rouf MA, Safia H, Farzana K, Khursheed A, Asif A (2015) Structural changes in histone H2A by methylglyoxal generate highly immunogenic amorphous aggregates with implications in auto-immune response in cancer. Glycobiology 26(2):129–141
53.
Zurück zum Zitat Saheem A, Kiran D, Uzma S, Khursheed A, Asif A (2011) Genotoxicity and immunogenicity of DNA-advanced glycation end products formed by methylglyoxal and lysine in presence of Cu2+. Biochem Biophys Res Commun 407(3):568–574CrossRef Saheem A, Kiran D, Uzma S, Khursheed A, Asif A (2011) Genotoxicity and immunogenicity of DNA-advanced glycation end products formed by methylglyoxal and lysine in presence of Cu2+. Biochem Biophys Res Commun 407(3):568–574CrossRef
55.
Zurück zum Zitat Uetz-von AE, Michael K, Günter F, Legler DF (2008) V domain of RAGE interacts with AGEs on prostate carcinoma cells. Prostate 68(7):748–758CrossRef Uetz-von AE, Michael K, Günter F, Legler DF (2008) V domain of RAGE interacts with AGEs on prostate carcinoma cells. Prostate 68(7):748–758CrossRef
56.
Zurück zum Zitat Rabbani Naila, Thornalley Paul J (2014). Dicarbonyl proteome and genome damage in metabolic and vascular disease. Biochem Soc Trans. Rabbani Naila, Thornalley Paul J (2014). Dicarbonyl proteome and genome damage in metabolic and vascular disease. Biochem Soc Trans.
57.
Zurück zum Zitat Deng R, Wu H, Hui R, Kong X, Hu L, Wang X, Qing S (2017) Glucose-derived AGEs promote migration and invasion of colorectal cancer by up-regulating Sp1 expression. BBA-Gen Subjects 1861(5):1065–1074CrossRef Deng R, Wu H, Hui R, Kong X, Hu L, Wang X, Qing S (2017) Glucose-derived AGEs promote migration and invasion of colorectal cancer by up-regulating Sp1 expression. BBA-Gen Subjects 1861(5):1065–1074CrossRef
58.
Zurück zum Zitat Shun-Yao K, Hshin-An K, Tzong-Ming S, Tzong-Cherng C, Chen H-I, Yi-Ting C, Yu Y-H, Yang S-H, Shu-Shing C (2017) Advanced glycation end products influence oral cancer cell survival via Bcl-xl and Nrf-2 regulation in vitro. Oncol Lett 13(5):3328–3334CrossRef Shun-Yao K, Hshin-An K, Tzong-Ming S, Tzong-Cherng C, Chen H-I, Yi-Ting C, Yu Y-H, Yang S-H, Shu-Shing C (2017) Advanced glycation end products influence oral cancer cell survival via Bcl-xl and Nrf-2 regulation in vitro. Oncol Lett 13(5):3328–3334CrossRef
59.
Zurück zum Zitat Jun-Ichi T, Sho-Ichi Y, Masayoshi T (2010) Cancer malignancy is enhanced by glyceraldehyde-derived advanced glycation end-products. J Oncol:2010 Jun-Ichi T, Sho-Ichi Y, Masayoshi T (2010) Cancer malignancy is enhanced by glyceraldehyde-derived advanced glycation end-products. J Oncol:2010
60.
Zurück zum Zitat Riichiro A, Sho-ichi Y (2008) AGE-RAGE system and carcinogenesis. Curr Pharm Des 14(10):940–945CrossRef Riichiro A, Sho-ichi Y (2008) AGE-RAGE system and carcinogenesis. Curr Pharm Des 14(10):940–945CrossRef
61.
Zurück zum Zitat Lin J-A, Wu C-H, Gow-Chin Y (2017) Methylglyoxal displays colorectal cancer-promoting properties in the murine models of azoxymethane and CT26 isografts. Free Radic Biol Med Lin J-A, Wu C-H, Gow-Chin Y (2017) Methylglyoxal displays colorectal cancer-promoting properties in the murine models of azoxymethane and CT26 isografts. Free Radic Biol Med
62.
Zurück zum Zitat Dachun Y, Michael B (2010) Hyperglycemia-induced reactive oxygen species increase expression of the receptor for advanced glycation end products (RAGE) and RAGE ligands. Diabetes 59(1):249–255CrossRef Dachun Y, Michael B (2010) Hyperglycemia-induced reactive oxygen species increase expression of the receptor for advanced glycation end products (RAGE) and RAGE ligands. Diabetes 59(1):249–255CrossRef
63.
Zurück zum Zitat Kuang CY, Rusliza B, Herni T, Hing TT, Norshariza N (2013) Receptor for advanced glycation end products and its involvement in inflammatory diseases. Int J Inflamm:2013 Kuang CY, Rusliza B, Herni T, Hing TT, Norshariza N (2013) Receptor for advanced glycation end products and its involvement in inflammatory diseases. Int J Inflamm:2013
64.
Zurück zum Zitat Christiane O, Kathleen J, Elisa H, Navarrete SA, Tilman G, Andreas S (2014) Role of advanced glycation end products in cellular signaling. Redox Biol 2:411–429CrossRef Christiane O, Kathleen J, Elisa H, Navarrete SA, Tilman G, Andreas S (2014) Role of advanced glycation end products in cellular signaling. Redox Biol 2:411–429CrossRef
65.
Zurück zum Zitat Christoffer G, Astrid R, Moritz D, Julia N, Gerhard F, Karin M-D, Alexander E, Bernd A, Bierhaus Angelika NPP (2008) RAGE signaling sustains inflammation and promotes tumor development. J Exp Med 205(2):275–285CrossRef Christoffer G, Astrid R, Moritz D, Julia N, Gerhard F, Karin M-D, Alexander E, Bernd A, Bierhaus Angelika NPP (2008) RAGE signaling sustains inflammation and promotes tumor development. J Exp Med 205(2):275–285CrossRef
66.
Zurück zum Zitat Barbel L-S, Markus S, Peter N, Angelika B (2007) RAGE signaling in cell adhesion and inflammation. Curr Pediatr Rev 3(1):1–9 Barbel L-S, Markus S, Peter N, Angelika B (2007) RAGE signaling in cell adhesion and inflammation. Curr Pediatr Rev 3(1):1–9
67.
Zurück zum Zitat Sparvero Louis J, Denise A-A, Rui K, Daolin T, Neilay A, Jaehyun I, Ronnye R, Lin Brenda AAA, Zeh Herbert J (2009) RAGE (Receptor for Advanced Glycation endproducts), RAGE ligands, and their role in cancer and inflammation. J Transl Med 7(1):17PubMedPubMedCentralCrossRef Sparvero Louis J, Denise A-A, Rui K, Daolin T, Neilay A, Jaehyun I, Ronnye R, Lin Brenda AAA, Zeh Herbert J (2009) RAGE (Receptor for Advanced Glycation endproducts), RAGE ligands, and their role in cancer and inflammation. J Transl Med 7(1):17PubMedPubMedCentralCrossRef
68.
Zurück zum Zitat Martinez-Outschoorn Ubaldo E, Curry Joseph M, Ying-Hui K, Lin Z, Madalina T, David C, Birbe Ruth C, Edmund P, Alessandro B, Pestell RG (2013) Oncogenes and inflammation rewire host energy metabolism in the tumor microenvironment: RAS and NFκB target stromal MCT4. Cell Cycle 12(16):2580–2597PubMedPubMedCentralCrossRef Martinez-Outschoorn Ubaldo E, Curry Joseph M, Ying-Hui K, Lin Z, Madalina T, David C, Birbe Ruth C, Edmund P, Alessandro B, Pestell RG (2013) Oncogenes and inflammation rewire host energy metabolism in the tumor microenvironment: RAS and NFκB target stromal MCT4. Cell Cycle 12(16):2580–2597PubMedPubMedCentralCrossRef
69.
Zurück zum Zitat Masson Norma RPJ (2014) Hypoxia signaling pathways in cancer metabolism: the importance of co-selecting interconnected physiological pathways. Cancer Metab 2(1):3PubMedPubMedCentralCrossRef Masson Norma RPJ (2014) Hypoxia signaling pathways in cancer metabolism: the importance of co-selecting interconnected physiological pathways. Cancer Metab 2(1):3PubMedPubMedCentralCrossRef
70.
Zurück zum Zitat Sina G, Christian V, Philipp S, Doris M (2012) Hypoxia and HIF-1 increase S100A8 and S100A9 expression in prostate cancer. Int J Cancer 131(12):2785–2794CrossRef Sina G, Christian V, Philipp S, Doris M (2012) Hypoxia and HIF-1 increase S100A8 and S100A9 expression in prostate cancer. Int J Cancer 131(12):2785–2794CrossRef
71.
Zurück zum Zitat Masuko U-F, Yoshimasa N (2008) Reactive oxygen species and angiogenesis: NADPH oxidase as target for cancer therapy. Cancer Lett 266(1):37–52CrossRef Masuko U-F, Yoshimasa N (2008) Reactive oxygen species and angiogenesis: NADPH oxidase as target for cancer therapy. Cancer Lett 266(1):37–52CrossRef
72.
Zurück zum Zitat Xuebo C, Leying Z, Zhang Ian Y, Junling L, Huaqing W, Mao O, Shihua W, Carvalho d FAC, Lihong W, Yasuhiko Y (2014) RAGE expression in tumor-associated macrophages promotes angiogenesis in glioma. Cancer Res 74(24):7285–7297CrossRef Xuebo C, Leying Z, Zhang Ian Y, Junling L, Huaqing W, Mao O, Shihua W, Carvalho d FAC, Lihong W, Yasuhiko Y (2014) RAGE expression in tumor-associated macrophages promotes angiogenesis in glioma. Cancer Res 74(24):7285–7297CrossRef
73.
Zurück zum Zitat Huasheng L, Yuhua Z, Shaobi Z, Liang P (2011) Knockdown of RAGE expression inhibits colorectal cancer cell invasion and suppresses angiogenesis in vitro and in vivo. Cancer Lett 313(1):91–98CrossRef Huasheng L, Yuhua Z, Shaobi Z, Liang P (2011) Knockdown of RAGE expression inhibits colorectal cancer cell invasion and suppresses angiogenesis in vitro and in vivo. Cancer Lett 313(1):91–98CrossRef
74.
Zurück zum Zitat Wang W, Luo H-S, Yu B-P (2004) Expression of NF-κB and human telomerase reverse transcriptase in gastric cancer and precancerous lesions. World J Gastroenterol 10(2):177PubMedPubMedCentralCrossRef Wang W, Luo H-S, Yu B-P (2004) Expression of NF-κB and human telomerase reverse transcriptase in gastric cancer and precancerous lesions. World J Gastroenterol 10(2):177PubMedPubMedCentralCrossRef
75.
Zurück zum Zitat Masaharu A, Teru H, Toshiaki H, Yu-Tzu T, Mitsiades Constantine S, Nicholas M, Dharminder C, Paul R, Munshi Nikhil C, Anderson Kenneth C (2003) Nuclear factor-κB p65 mediates tumor necrosis factor α-induced nuclear translocation of telomerase reverse transcriptase protein. Cancer Res 63(1):18–21 Masaharu A, Teru H, Toshiaki H, Yu-Tzu T, Mitsiades Constantine S, Nicholas M, Dharminder C, Paul R, Munshi Nikhil C, Anderson Kenneth C (2003) Nuclear factor-κB p65 mediates tumor necrosis factor α-induced nuclear translocation of telomerase reverse transcriptase protein. Cancer Res 63(1):18–21
76.
Zurück zum Zitat Chung LK, Vinay T (2013) Telomerase: central regulator of all of the hallmarks of cancer. Trends Biochem Sci 38(9):426–434CrossRef Chung LK, Vinay T (2013) Telomerase: central regulator of all of the hallmarks of cancer. Trends Biochem Sci 38(9):426–434CrossRef
77.
Zurück zum Zitat Lipinska Natalia, Romaniuk Aleksandra, Paszel-Jaworska Anna, Toton Ewa, Kopczynski Przemyslaw, Rubis Blazej. 2017. Telomerase and drug resistance in cancer. Cell Mol Life Sci:1–12 Lipinska Natalia, Romaniuk Aleksandra, Paszel-Jaworska Anna, Toton Ewa, Kopczynski Przemyslaw, Rubis Blazej. 2017. Telomerase and drug resistance in cancer. Cell Mol Life Sci:1–12
78.
Zurück zum Zitat Wang Julie C, Bennett Martin R. 2010. Nuclear factor-κΒ-mediated regulation of telomerase. Am Heart Assoc Wang Julie C, Bennett Martin R. 2010. Nuclear factor-κΒ-mediated regulation of telomerase. Am Heart Assoc
79.
80.
Zurück zum Zitat Julio M, Li L, Fattah Farjana J, Ying D, Bey Erik A, Malina P, Jinming G, Boothman David A (2014) Review of poly(ADP-ribose) polymerase (PARP) mechanisms of action and rationale for targeting in cancer and other diseases. Crit Rev Eukaryot Gene Expr 24(1) Julio M, Li L, Fattah Farjana J, Ying D, Bey Erik A, Malina P, Jinming G, Boothman David A (2014) Review of poly(ADP-ribose) polymerase (PARP) mechanisms of action and rationale for targeting in cancer and other diseases. Crit Rev Eukaryot Gene Expr 24(1)
81.
Zurück zum Zitat Srikrishna Geetha FHH (2009) Endogenous damage-associated molecular pattern molecules at the crossroads of inflammation and cancer. Neoplasia 11(7):615–628PubMedPubMedCentralCrossRef Srikrishna Geetha FHH (2009) Endogenous damage-associated molecular pattern molecules at the crossroads of inflammation and cancer. Neoplasia 11(7):615–628PubMedPubMedCentralCrossRef
82.
Zurück zum Zitat Dara D, Wei-Xing Z, Thompson Craig B (2007) Activation of poly (ADP)-ribose polymerase (PARP-1) induces release of the pro-inflammatory mediator HMGB1 from the nucleus. J Biol Chem 282(24):17845–17854CrossRef Dara D, Wei-Xing Z, Thompson Craig B (2007) Activation of poly (ADP)-ribose polymerase (PARP-1) induces release of the pro-inflammatory mediator HMGB1 from the nucleus. J Biol Chem 282(24):17845–17854CrossRef
83.
Zurück zum Zitat Kang Rui, Xie Yangchun, Zhang Qiuhong, Hou Wen, Jiang Qingping, Zhu Shan, Liu Jinbao, Zeng Dexing, Wang Haichao, Bartlett David L. 2017. Intracellular HMGB1 as a novel tumor suppressor of pancreatic cancer. Cell Res Kang Rui, Xie Yangchun, Zhang Qiuhong, Hou Wen, Jiang Qingping, Zhu Shan, Liu Jinbao, Zeng Dexing, Wang Haichao, Bartlett David L. 2017. Intracellular HMGB1 as a novel tumor suppressor of pancreatic cancer. Cell Res
84.
Zurück zum Zitat Rui K, Qiuhong Z, Zeh Herbert J, Lotze Michael T, Daolin T (2013) HMGB1 in cancer: good, bad, or both? Clin Cancer Res 19(15):4046–4057CrossRef Rui K, Qiuhong Z, Zeh Herbert J, Lotze Michael T, Daolin T (2013) HMGB1 in cancer: good, bad, or both? Clin Cancer Res 19(15):4046–4057CrossRef
85.
Zurück zum Zitat Rui K, Daolin T, Schapiro Nicole E, Livesey Kristen M, Adam F, Patricia L, Angelika B, Lotze Michael T, Zeh Herbert J (2010) The receptor for advanced glycation end products (RAGE) sustains autophagy and limits apoptosis, promoting pancreatic tumor cell survival. Cell Death Differ 17(4):666–676CrossRef Rui K, Daolin T, Schapiro Nicole E, Livesey Kristen M, Adam F, Patricia L, Angelika B, Lotze Michael T, Zeh Herbert J (2010) The receptor for advanced glycation end products (RAGE) sustains autophagy and limits apoptosis, promoting pancreatic tumor cell survival. Cell Death Differ 17(4):666–676CrossRef
86.
Zurück zum Zitat Leclerc Estelle, Vetter Stefan W. 2015. The role of S100 proteins and their receptor RAGE in pancreatic cancer. BBA-Mol Basis Dis 1852 (12):2706–2711 Leclerc Estelle, Vetter Stefan W. 2015. The role of S100 proteins and their receptor RAGE in pancreatic cancer. BBA-Mol Basis Dis 1852 (12):2706–2711
88.
Zurück zum Zitat Chonggao Y, Hongli L, Baogang Z, Yuqing L, Guohua L, Shijun L, Lei S, Yueliang Q, Xiaolong L, Weiyi C (2013) RAGE-binding S100A8/A9 promotes the migration and invasion of human breast cancer cells through actin polymerization and epithelial–mesenchymal transition. Breast Cancer Res Treat 142(2):297–309CrossRef Chonggao Y, Hongli L, Baogang Z, Yuqing L, Guohua L, Shijun L, Lei S, Yueliang Q, Xiaolong L, Weiyi C (2013) RAGE-binding S100A8/A9 promotes the migration and invasion of human breast cancer cells through actin polymerization and epithelial–mesenchymal transition. Breast Cancer Res Treat 142(2):297–309CrossRef
89.
Zurück zum Zitat Akihiko T, Blood David C, del Toro G, Anthony C, Lee Daniel C, Qu W, Nozomu T, Yan L, Evanthia L, Caifeng F (2000) Blockade of RAGE–amphoterin signalling suppresses tumour growth and metastases. Nature 405(6784):354–360CrossRef Akihiko T, Blood David C, del Toro G, Anthony C, Lee Daniel C, Qu W, Nozomu T, Yan L, Evanthia L, Caifeng F (2000) Blockade of RAGE–amphoterin signalling suppresses tumour growth and metastases. Nature 405(6784):354–360CrossRef
90.
Zurück zum Zitat Dakhel S, Padilla L, Adan J, Masa M, Martinez JM, Roque L, Coll T, Hervas R, Calvis C, Messeguer R (2014) S100P antibody-mediated therapy as a new promising strategy for the treatment of pancreatic cancer. Oncogenesis 3(3):e92PubMedPubMedCentralCrossRef Dakhel S, Padilla L, Adan J, Masa M, Martinez JM, Roque L, Coll T, Hervas R, Calvis C, Messeguer R (2014) S100P antibody-mediated therapy as a new promising strategy for the treatment of pancreatic cancer. Oncogenesis 3(3):e92PubMedPubMedCentralCrossRef
91.
Zurück zum Zitat Hudson BI, Kalea AZ, del Mar AM, Harja E, Boulanger E, Vivette D'A, Schmidt AM (2008) Interaction of the RAGE cytoplasmic domain with diaphanous-1 is required for ligand-stimulated cellular migration through activation of Rac1 and Cdc42. J Biol Chem 283(49):34457–34468PubMedPubMedCentralCrossRef Hudson BI, Kalea AZ, del Mar AM, Harja E, Boulanger E, Vivette D'A, Schmidt AM (2008) Interaction of the RAGE cytoplasmic domain with diaphanous-1 is required for ligand-stimulated cellular migration through activation of Rac1 and Cdc42. J Biol Chem 283(49):34457–34468PubMedPubMedCentralCrossRef
92.
Zurück zum Zitat Martini M, De Santis MC, Braccinik L, Gulluni F, Hirsch E (2014) PI3K/AKT signaling pathway and cancer: an updated review. Ann Med 46(6):372–383PubMedCrossRef Martini M, De Santis MC, Braccinik L, Gulluni F, Hirsch E (2014) PI3K/AKT signaling pathway and cancer: an updated review. Ann Med 46(6):372–383PubMedCrossRef
93.
Zurück zum Zitat AL-Madhagi R, AL-Madhagi Y, Ma X, Juan Z, Cejun Y, Qiong D, Pengfei R, Ye B, Sheng L, Wei W (2013) Specific siRNA targeting receptor for advanced glycation end products (RAGE) decreases proliferation in human breast cancer cell lines. Int J Mol Sci 14(4):7959–7978CrossRef AL-Madhagi R, AL-Madhagi Y, Ma X, Juan Z, Cejun Y, Qiong D, Pengfei R, Ye B, Sheng L, Wei W (2013) Specific siRNA targeting receptor for advanced glycation end products (RAGE) decreases proliferation in human breast cancer cell lines. Int J Mol Sci 14(4):7959–7978CrossRef
94.
Zurück zum Zitat Roberts Patrick J, Der Channing J (2007) Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer. Oncogene 26(22):3291–3310CrossRef Roberts Patrick J, Der Channing J (2007) Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer. Oncogene 26(22):3291–3310CrossRef
95.
Zurück zum Zitat Sylvain M, Jacques P (2007) The ERK1/2 mitogen-activated protein kinase pathway as a master regulator of the G1-to S-phase transition. Oncogene 26(22):3227–3239CrossRef Sylvain M, Jacques P (2007) The ERK1/2 mitogen-activated protein kinase pathway as a master regulator of the G1-to S-phase transition. Oncogene 26(22):3227–3239CrossRef
96.
Zurück zum Zitat San-Cher C, Jinn-Yuh G, Chi-Ching H, Shean-Jaw C, Tai-Du L, Yu-Ming K, Jau-Shyang H, Yu-Lin Y, Lea-Yea C (2010) Advanced glycation end-products activate extracellular signal-regulated kinase via the oxidative stress-EGF receptor pathway in renal fibroblasts. Journal of Cellular Biochemistry 109(1):38–48 San-Cher C, Jinn-Yuh G, Chi-Ching H, Shean-Jaw C, Tai-Du L, Yu-Ming K, Jau-Shyang H, Yu-Lin Y, Lea-Yea C (2010) Advanced glycation end-products activate extracellular signal-regulated kinase via the oxidative stress-EGF receptor pathway in renal fibroblasts. Journal of Cellular Biochemistry 109(1):38–48
97.
Zurück zum Zitat Qiu-Yu Z, Lin-Qing W, Zhang T, Yan-Fei H, Xu L (2015) Autophagy-mediated HMGB1 release promotes gastric cancer cell survival via RAGE activation of extracellular signal-regulated kinases 1/2. Oncol Rep 33(4):1630–1638CrossRef Qiu-Yu Z, Lin-Qing W, Zhang T, Yan-Fei H, Xu L (2015) Autophagy-mediated HMGB1 release promotes gastric cancer cell survival via RAGE activation of extracellular signal-regulated kinases 1/2. Oncol Rep 33(4):1630–1638CrossRef
98.
Zurück zum Zitat Thiruvengadam A, Logsdon Craig D (2011) S100P: a novel therapeutic target for cancer. Amino Acids 41(4):893–899CrossRef Thiruvengadam A, Logsdon Craig D (2011) S100P: a novel therapeutic target for cancer. Amino Acids 41(4):893–899CrossRef
99.
Zurück zum Zitat Holger Z, Stephan B, Thomas H, Jochen H, Oliver F, Michael L, Bernd W, Erbersdobler Helmut F, Sabine S, Busch Andreas E (2003) RAGE-mediated MAPK activation by food-derived AGE and non-AGE products. Biochem Biophys Res Commun 300(2):311–315CrossRef Holger Z, Stephan B, Thomas H, Jochen H, Oliver F, Michael L, Bernd W, Erbersdobler Helmut F, Sabine S, Busch Andreas E (2003) RAGE-mediated MAPK activation by food-derived AGE and non-AGE products. Biochem Biophys Res Commun 300(2):311–315CrossRef
100.
Zurück zum Zitat Kwak Taekyoung D-EK, Ergonul A, Miller PC, Braley A, Hwang GH, Zhao D, Besser A, Yamamoto Y, Yamamoto H (2017) Targeting of RAGE-ligand signaling impairs breast cancer cell invasion and metastasis. Oncogene 36(11):1559–1572CrossRef Kwak Taekyoung D-EK, Ergonul A, Miller PC, Braley A, Hwang GH, Zhao D, Besser A, Yamamoto Y, Yamamoto H (2017) Targeting of RAGE-ligand signaling impairs breast cancer cell invasion and metastasis. Oncogene 36(11):1559–1572CrossRef
101.
Zurück zum Zitat Indira E, Sivasakthivel T, Aoshuang C, Guoxing Z, Bosland Maarten C, André K-B, Munirathinam G (2012) Targeting receptor for advanced glycation end products (RAGE) expression induces apoptosis and inhibits prostate tumor growth. Biochem Biophys Res Commun 417(4):1133–1138CrossRef Indira E, Sivasakthivel T, Aoshuang C, Guoxing Z, Bosland Maarten C, André K-B, Munirathinam G (2012) Targeting receptor for advanced glycation end products (RAGE) expression induces apoptosis and inhibits prostate tumor growth. Biochem Biophys Res Commun 417(4):1133–1138CrossRef
102.
Zurück zum Zitat Ganju Ramesh K. 2013. Receptor for advanced glycation end products (RAGE) as a novel target for inhibiting breast cancer bone metastasis. Ohio state univ columbus Ganju Ramesh K. 2013. Receptor for advanced glycation end products (RAGE) as a novel target for inhibiting breast cancer bone metastasis. Ohio state univ columbus
103.
Zurück zum Zitat Fara B-M, Simone F, Steven C, Rebecca M, Jelmar Q, Erika F-D, Plumb Darren A, Leila Z, Patrycja G, Gianmaria L (2016) PIM1 kinase regulates cell death, tumor growth and chemotherapy response in triple-negative breast cancer. Nat Med 22(11):1303–1313CrossRef Fara B-M, Simone F, Steven C, Rebecca M, Jelmar Q, Erika F-D, Plumb Darren A, Leila Z, Patrycja G, Gianmaria L (2016) PIM1 kinase regulates cell death, tumor growth and chemotherapy response in triple-negative breast cancer. Nat Med 22(11):1303–1313CrossRef
104.
Zurück zum Zitat Hardaway Aimalie L, Izabela P (2013) IL-1β, RAGE and FABP4: targeting the dynamic trio in metabolic inflammation and related pathologies. Future Med Chem 5(10):1089–1108PubMedCrossRef Hardaway Aimalie L, Izabela P (2013) IL-1β, RAGE and FABP4: targeting the dynamic trio in metabolic inflammation and related pathologies. Future Med Chem 5(10):1089–1108PubMedCrossRef
106.
Zurück zum Zitat Matsubara D, Niki T, Ishikawa S, Goto A, Ohara E, Yokomizo T, Heizmann CW, Aburatani H, Moriyama S, Moriyama H, Nishimura Y, Funata N, Fukayama M (2005) Differential expression of S100A2 and S100A4 in lung adenocarcinomas: clinicopathological significance, relationship to p53 and identification of their target genes. Cancer Sci 96(12):844–857. https://doi.org/10.1111/j.1349-7006.2005.00121.x PubMedCrossRef Matsubara D, Niki T, Ishikawa S, Goto A, Ohara E, Yokomizo T, Heizmann CW, Aburatani H, Moriyama S, Moriyama H, Nishimura Y, Funata N, Fukayama M (2005) Differential expression of S100A2 and S100A4 in lung adenocarcinomas: clinicopathological significance, relationship to p53 and identification of their target genes. Cancer Sci 96(12):844–857. https://​doi.​org/​10.​1111/​j.​1349-7006.​2005.​00121.​x PubMedCrossRef
108.
Zurück zum Zitat Elena C, Carla C, Annalisa M, Samanta T, Youssef S, Marcella P, Alessandra D’a, Caterina S, Giovanni S, Rosario C (2015) S100B-p53 disengagement by pentamidine promotes apoptosis and inhibits cellular migration via aquaporin-4 and metalloproteinase-2 inhibition in C6 glioma cells. Oncology Letters 9(6):2864–2870CrossRef Elena C, Carla C, Annalisa M, Samanta T, Youssef S, Marcella P, Alessandra D’a, Caterina S, Giovanni S, Rosario C (2015) S100B-p53 disengagement by pentamidine promotes apoptosis and inhibits cellular migration via aquaporin-4 and metalloproteinase-2 inhibition in C6 glioma cells. Oncology Letters 9(6):2864–2870CrossRef
109.
Zurück zum Zitat Jing L, Qingyuan Y, Wilder Paul T, France C, Weber David J (2010) The calcium-binding protein S100B down-regulates p53 and apoptosis in malignant melanoma. J Biol Chem 285(35):27487–27498CrossRef Jing L, Qingyuan Y, Wilder Paul T, France C, Weber David J (2010) The calcium-binding protein S100B down-regulates p53 and apoptosis in malignant melanoma. J Biol Chem 285(35):27487–27498CrossRef
110.
Zurück zum Zitat Luis HJ, Laura P, Sheila D, Toni C, Rosa H, Jaume A, Marc M, Francesc M, Maria MJ, Silvia C (2013) Therapeutic targeting of tumor growth and angiogenesis with a novel anti-S100A4 monoclonal antibody. PLoS One 8(9):e72480CrossRef Luis HJ, Laura P, Sheila D, Toni C, Rosa H, Jaume A, Marc M, Francesc M, Maria MJ, Silvia C (2013) Therapeutic targeting of tumor growth and angiogenesis with a novel anti-S100A4 monoclonal antibody. PLoS One 8(9):e72480CrossRef
111.
Zurück zum Zitat Lu Z, Da L, Yi-Ming Z, Yang H, Cheng D, Ma X-X (2016) Effects of receptor for advanced glycation endproducts on microvessel formation in endometrial cancer. BMC Cancer 16(1):93CrossRef Lu Z, Da L, Yi-Ming Z, Yang H, Cheng D, Ma X-X (2016) Effects of receptor for advanced glycation endproducts on microvessel formation in endometrial cancer. BMC Cancer 16(1):93CrossRef
112.
Zurück zum Zitat June C, Koo LM, Kyoung Ho O, Soo KY, Young CH, Kuk BS, Yoon JK, Jeong-Soo W, Hoon LS, Young KS (2011) Interaction effect between the receptor for advanced glycation end products (RAGE) and high-mobility group box-1 (HMGB-1) for the migration of a squamous cell carcinoma cell line. Tumori 97(2):196–202CrossRef June C, Koo LM, Kyoung Ho O, Soo KY, Young CH, Kuk BS, Yoon JK, Jeong-Soo W, Hoon LS, Young KS (2011) Interaction effect between the receptor for advanced glycation end products (RAGE) and high-mobility group box-1 (HMGB-1) for the migration of a squamous cell carcinoma cell line. Tumori 97(2):196–202CrossRef
113.
Zurück zum Zitat Lu Xin HJW, Erin P, Xiaoying S, Patricia T, Pingna D, Shan J, Qing C, Spring Denise J, Padmanee S (2017) Effective combinatorial immunotherapy for castration-resistant prostate cancer. Nature 543(7647):728–732PubMedPubMedCentralCrossRef Lu Xin HJW, Erin P, Xiaoying S, Patricia T, Pingna D, Shan J, Qing C, Spring Denise J, Padmanee S (2017) Effective combinatorial immunotherapy for castration-resistant prostate cancer. Nature 543(7647):728–732PubMedPubMedCentralCrossRef
114.
Zurück zum Zitat Joseph M, Carson William E (2013) Review of S100A9 biology and its role in cancer. BBA-Rev Cancer 1835(1):100–109 Joseph M, Carson William E (2013) Review of S100A9 biology and its role in cancer. BBA-Rev Cancer 1835(1):100–109
115.
Zurück zum Zitat Ren X, Shao H, Wei Q, Sun Z, Liu N (2009) Advanced glycation end-products enhance calcification in vascular smooth muscle cells. J Int Med Res 37(3):847–854PubMedCrossRef Ren X, Shao H, Wei Q, Sun Z, Liu N (2009) Advanced glycation end-products enhance calcification in vascular smooth muscle cells. J Int Med Res 37(3):847–854PubMedCrossRef
116.
Zurück zum Zitat Yukiko N, Yuji I, Yuka H, Jun-ichi K, Toshihiko N (2013) Advanced glycation end-products enhance calcification in cultured rat dental pulp cells. J Endod 39(7):873–878CrossRef Yukiko N, Yuji I, Yuka H, Jun-ichi K, Toshihiko N (2013) Advanced glycation end-products enhance calcification in cultured rat dental pulp cells. J Endod 39(7):873–878CrossRef
118.
Zurück zum Zitat Yoray S, Yael R, Noam C, Amir B-S, Hila S, Tamar G, Neta E (2015) Tumor-derived osteopontin reprograms normal mammary fibroblasts to promote inflammation and tumor growth in breast cancer. Cancer Res 75(6):963–973CrossRef Yoray S, Yael R, Noam C, Amir B-S, Hila S, Tamar G, Neta E (2015) Tumor-derived osteopontin reprograms normal mammary fibroblasts to promote inflammation and tumor growth in breast cancer. Cancer Res 75(6):963–973CrossRef
119.
Zurück zum Zitat Vijayanirmala S, Muthukumar T, Malathi N, Rajan ST (2015) OPN—revisited. Journal of Clinical and Diagnostic Research: JCDR 9(6):ZE10 Vijayanirmala S, Muthukumar T, Malathi N, Rajan ST (2015) OPN—revisited. Journal of Clinical and Diagnostic Research: JCDR 9(6):ZE10
121.
Zurück zum Zitat Weber Cynthia E, Kothari Anai N, Wai Philip Y, Li Neill Y, Joseph D, Zapf Matthew AC, Franzen Carrie A, Gupta Gopal N, Clodio O, Andrei Z (2015) Osteopontin mediates an MZF1–TGF-β1-dependent transformation of mesenchymal stem cells into cancer-associated fibroblasts in breast cancer. Oncogene 34(37):4821–4833CrossRef Weber Cynthia E, Kothari Anai N, Wai Philip Y, Li Neill Y, Joseph D, Zapf Matthew AC, Franzen Carrie A, Gupta Gopal N, Clodio O, Andrei Z (2015) Osteopontin mediates an MZF1–TGF-β1-dependent transformation of mesenchymal stem cells into cancer-associated fibroblasts in breast cancer. Oncogene 34(37):4821–4833CrossRef
123.
Zurück zum Zitat Saleh S, Thompson DE, McConkey J, Murray P, Moorehead RA (2016) Osteopontin regulates proliferation, apoptosis, and migration of murine claudin-low mammary tumor cells. BMC Cancer 16(1):359PubMedPubMedCentralCrossRef Saleh S, Thompson DE, McConkey J, Murray P, Moorehead RA (2016) Osteopontin regulates proliferation, apoptosis, and migration of murine claudin-low mammary tumor cells. BMC Cancer 16(1):359PubMedPubMedCentralCrossRef
124.
Zurück zum Zitat Dhanashri T, Asutosh S, Reeti B, Kirti L, Sanjay D, Anupama M, Swapnil K, Suhaschandra D, Kundu Gopal C (2013) Association of osteopontin and cyclooxygenase-2 expression with breast cancer subtypes and their use as potential biomarkers. Oncol Lett 6(6):1559–1564CrossRef Dhanashri T, Asutosh S, Reeti B, Kirti L, Sanjay D, Anupama M, Swapnil K, Suhaschandra D, Kundu Gopal C (2013) Association of osteopontin and cyclooxygenase-2 expression with breast cancer subtypes and their use as potential biomarkers. Oncol Lett 6(6):1559–1564CrossRef
125.
Zurück zum Zitat Bramwell Vivien HC, Tuck Alan B, Chapman Judith-Anne W, Anborgh Pieter H, Postenka Carl O, Waleed A-K, Shepherd Lois E, Lei H, Wilson Carolyn F, Pritchard KI (2014) Assessment of osteopontin in early breast cancer: correlative study in a randomised clinical trial. Breast Cancer Res 16(1):R8PubMedPubMedCentralCrossRef Bramwell Vivien HC, Tuck Alan B, Chapman Judith-Anne W, Anborgh Pieter H, Postenka Carl O, Waleed A-K, Shepherd Lois E, Lei H, Wilson Carolyn F, Pritchard KI (2014) Assessment of osteopontin in early breast cancer: correlative study in a randomised clinical trial. Breast Cancer Res 16(1):R8PubMedPubMedCentralCrossRef
126.
Zurück zum Zitat Bramwell Vivien HC, Doig Gordon S, Tuck Alan B, Wilson Sylvia M, Tonkin Katia S, Anna T, Francisco P, Vandenberg Theodore A, Chambers Ann F (2006) Serial plasma osteopontin levels have prognostic value in metastatic breast cancer. Clin Cancer Res 12(11):3337–3343PubMedCrossRef Bramwell Vivien HC, Doig Gordon S, Tuck Alan B, Wilson Sylvia M, Tonkin Katia S, Anna T, Francisco P, Vandenberg Theodore A, Chambers Ann F (2006) Serial plasma osteopontin levels have prognostic value in metastatic breast cancer. Clin Cancer Res 12(11):3337–3343PubMedCrossRef
127.
Zurück zum Zitat Abu E-AAM, Luc M, Karel G (2011) Expression of high-mobility groups box-1/receptor for advanced glycation end products/osteopontin/early growth response-1 pathway in proliferative vitreoretinal epiretinal membranes. Mol Vis 17:508 Abu E-AAM, Luc M, Karel G (2011) Expression of high-mobility groups box-1/receptor for advanced glycation end products/osteopontin/early growth response-1 pathway in proliferative vitreoretinal epiretinal membranes. Mol Vis 17:508
128.
Zurück zum Zitat Borthwick Lee A, Mann Derek A (2016) Liver: osteopontin and HMGB1: novel regulators of HSC activation. Nat Rev Gastroenterol Hepatol 13(6):320–322PubMedCrossRef Borthwick Lee A, Mann Derek A (2016) Liver: osteopontin and HMGB1: novel regulators of HSC activation. Nat Rev Gastroenterol Hepatol 13(6):320–322PubMedCrossRef
129.
Zurück zum Zitat Elena A, Ge X, Tung-Ming L, Fernando M, Aritz L, Yongke L, Naoto K, Raquel U, Neil T, Antoine Daniel J (2016) Signalling via the osteopontin and high mobility group box-1 axis drives the fibrogenic response to liver injury. In: Gut:gutjnl-2015-310752 Elena A, Ge X, Tung-Ming L, Fernando M, Aritz L, Yongke L, Naoto K, Raquel U, Neil T, Antoine Daniel J (2016) Signalling via the osteopontin and high mobility group box-1 axis drives the fibrogenic response to liver injury. In: Gut:gutjnl-2015-310752
130.
131.
Zurück zum Zitat Das Riku MGH, Kundu Gopal C (2003) Osteopontin stimulates cell motility and nuclear factor κB-mediated secretion of urokinase type plasminogen activator through phosphatidylinositol 3-kinase/Akt signaling pathways in breast cancer cells. J Biol Chem 278(31):28593–28606PubMedCrossRef Das Riku MGH, Kundu Gopal C (2003) Osteopontin stimulates cell motility and nuclear factor κB-mediated secretion of urokinase type plasminogen activator through phosphatidylinositol 3-kinase/Akt signaling pathways in breast cancer cells. J Biol Chem 278(31):28593–28606PubMedCrossRef
132.
Zurück zum Zitat Fernando O-M, Elena S, Eloy P-N, Ariadna P-B, Leire A, José S-P, Aranda Francisco I, Enrique L, Gloria P (2015) Osteopontin regulates VEGFA and ICAM-1 mRNA expression in breast carcinoma. Am J Clin Pathol 143(6):812–822CrossRef Fernando O-M, Elena S, Eloy P-N, Ariadna P-B, Leire A, José S-P, Aranda Francisco I, Enrique L, Gloria P (2015) Osteopontin regulates VEGFA and ICAM-1 mRNA expression in breast carcinoma. Am J Clin Pathol 143(6):812–822CrossRef
133.
Zurück zum Zitat Monalisa B, Anuradha B, Ramesh B, Goutam C, Priyanka G, Pompom G, Mahadeo G, Smita K, Dhiraj K, Santosh K (2014) Osteopontin as a therapeutic target for cancer. Expert Opin Ther Targets 18(8):883–895CrossRef Monalisa B, Anuradha B, Ramesh B, Goutam C, Priyanka G, Pompom G, Mahadeo G, Smita K, Dhiraj K, Santosh K (2014) Osteopontin as a therapeutic target for cancer. Expert Opin Ther Targets 18(8):883–895CrossRef
134.
Zurück zum Zitat Mansoor A, Kundu Gopal C (2010) Osteopontin selectively regulates p70S6K/mTOR phosphorylation leading to NF-κB dependent AP-1-mediated ICAM-1 expression in breast cancer cells. Mol Cancer 9(1):101 Mansoor A, Kundu Gopal C (2010) Osteopontin selectively regulates p70S6K/mTOR phosphorylation leading to NF-κB dependent AP-1-mediated ICAM-1 expression in breast cancer cells. Mol Cancer 9(1):101
135.
Zurück zum Zitat Reeti B, Vinit K, Kirti L, Swapnil K, Kundu Gopal C (2009) Activation of JAK2/STAT3 signaling by osteopontin promotes tumor growth in human breast cancer cells. Carcinogenesis 31(2):192–200 Reeti B, Vinit K, Kirti L, Swapnil K, Kundu Gopal C (2009) Activation of JAK2/STAT3 signaling by osteopontin promotes tumor growth in human breast cancer cells. Carcinogenesis 31(2):192–200
136.
Zurück zum Zitat Goutam C, Shalini J, Reeti B, Mansoor A, Priyanka S, Vinit K, Kundu Gopal C (2006) The multifaceted roles of osteopontin in cell signaling, tumor progression and angiogenesis. Curr Mol Med 6(8):819–830CrossRef Goutam C, Shalini J, Reeti B, Mansoor A, Priyanka S, Vinit K, Kundu Gopal C (2006) The multifaceted roles of osteopontin in cell signaling, tumor progression and angiogenesis. Curr Mol Med 6(8):819–830CrossRef
137.
Zurück zum Zitat Riku D, Mahabeleshwar Ganapati H, Kundu Gopal C (2004) Osteopontin induces AP-1-mediated secretion of urokinase-type plasminogen activator through c-Src-dependent epidermal growth factor receptor transactivation in breast cancer cells. J Biol Chem 279(12):11051–11064CrossRef Riku D, Mahabeleshwar Ganapati H, Kundu Gopal C (2004) Osteopontin induces AP-1-mediated secretion of urokinase-type plasminogen activator through c-Src-dependent epidermal growth factor receptor transactivation in breast cancer cells. J Biol Chem 279(12):11051–11064CrossRef
138.
Zurück zum Zitat Antje H, Henri W, Matthias K, Matthias K, Dirk V, Helge T, Matthias B (2010) Effects of osteopontin inhibition on radiosensitivityof MDA-MB-231 breast cancer cells. Radiat Oncol 5(1):82CrossRef Antje H, Henri W, Matthias K, Matthias K, Dirk V, Helge T, Matthias B (2010) Effects of osteopontin inhibition on radiosensitivityof MDA-MB-231 breast cancer cells. Radiat Oncol 5(1):82CrossRef
140.
Zurück zum Zitat Atkinson RL, Yang WT, Rosen DG, Landis MD, Wong H, Lewis MT, Creighton CJ, Sexton KR, Hilsenbeck SG, Sahin AA, Brewster AM, Woodward WA, Chang JC (2013) Cancer stem cell markers are enriched in normal tissue adjacent to triple negative breast cancer and inversely correlated with DNA repair deficiency. Breast Cancer Research BCR 15(5):R77. https://doi.org/10.1186/bcr3471 PubMedPubMedCentralCrossRef Atkinson RL, Yang WT, Rosen DG, Landis MD, Wong H, Lewis MT, Creighton CJ, Sexton KR, Hilsenbeck SG, Sahin AA, Brewster AM, Woodward WA, Chang JC (2013) Cancer stem cell markers are enriched in normal tissue adjacent to triple negative breast cancer and inversely correlated with DNA repair deficiency. Breast Cancer Research BCR 15(5):R77. https://​doi.​org/​10.​1186/​bcr3471 PubMedPubMedCentralCrossRef
141.
Zurück zum Zitat Stephen P (1889) The distribution of secondary growths in cancer of the breast. Lancet 133(3421):571–573CrossRef Stephen P (1889) The distribution of secondary growths in cancer of the breast. Lancet 133(3421):571–573CrossRef
142.
Zurück zum Zitat Mikuła-Pietrasik J, Paweł U, Andrzej T, Krzysztof K (2017) The peritoneal “soil” for a cancerous “seed”: a comprehensive review of the pathogenesis of intraperitoneal cancer metastases. Cell Mol Life Sci:1–17 Mikuła-Pietrasik J, Paweł U, Andrzej T, Krzysztof K (2017) The peritoneal “soil” for a cancerous “seed”: a comprehensive review of the pathogenesis of intraperitoneal cancer metastases. Cell Mol Life Sci:1–17
143.
Zurück zum Zitat Thomas K, Emilia W, Sabine H-K, Ande Sudharsana R, Sebastian W, Klaus S-O, Marek L (2008) Cancer stem cell markers in common cancers—therapeutic implications. Trends Mol Med 14(10):450–460CrossRef Thomas K, Emilia W, Sabine H-K, Ande Sudharsana R, Sebastian W, Klaus S-O, Marek L (2008) Cancer stem cell markers in common cancers—therapeutic implications. Trends Mol Med 14(10):450–460CrossRef
145.
Zurück zum Zitat Yong L, Wang W-M, Xue-Lin Z, He H-Q, Xiao-Lei S, Hong Z, Xu X-F, Liang H, Zhu Z, Lei Z (2016) AGE/RAGE promotes thecalcification of human aortic smooth muscle cells via the Wnt/β-catenin axis. Am J Transl Res 8(11):4644 Yong L, Wang W-M, Xue-Lin Z, He H-Q, Xiao-Lei S, Hong Z, Xu X-F, Liang H, Zhu Z, Lei Z (2016) AGE/RAGE promotes thecalcification of human aortic smooth muscle cells via the Wnt/β-catenin axis. Am J Transl Res 8(11):4644
146.
Zurück zum Zitat Ulrike S, Franziska A, Janice S, Ulrike S, Pia H, Wolfgang W, Margit L, Iduna F, Shoemaker Robert H, Schlag Peter M (2011) Intervening in β-catenin signaling by sulindac inhibits S100A4-dependent colon cancer metastasis. Neoplasia 13(2):131–IN138CrossRef Ulrike S, Franziska A, Janice S, Ulrike S, Pia H, Wolfgang W, Margit L, Iduna F, Shoemaker Robert H, Schlag Peter M (2011) Intervening in β-catenin signaling by sulindac inhibits S100A4-dependent colon cancer metastasis. Neoplasia 13(2):131–IN138CrossRef
147.
Zurück zum Zitat Ulrike S, Wolfgang W, Dominic S, Mike S, Jutta A, Clara L, Fichtner Iduna SPM, Shoemaker Robert H, Ulrike S (2011) S100A4-induced cell motility and metastasis is restricted by the Wnt/β-catenin pathway inhibitor calcimycin in colon cancer cells. Mol Biol Cell 22(18):3344–3354CrossRef Ulrike S, Wolfgang W, Dominic S, Mike S, Jutta A, Clara L, Fichtner Iduna SPM, Shoemaker Robert H, Ulrike S (2011) S100A4-induced cell motility and metastasis is restricted by the Wnt/β-catenin pathway inhibitor calcimycin in colon cancer cells. Mol Biol Cell 22(18):3344–3354CrossRef
148.
Zurück zum Zitat Dexing F, David H, Yanhua Z, Yan X, Jill M, Heinz N, Mills Gordon B, Ryuji K, Tony H, Zhimin L (2007) Phosphorylation of β-catenin by AKT promotes β-catenin transcriptional activity. J Biol Chem 282(15):11221–11229CrossRef Dexing F, David H, Yanhua Z, Yan X, Jill M, Heinz N, Mills Gordon B, Ryuji K, Tony H, Zhimin L (2007) Phosphorylation of β-catenin by AKT promotes β-catenin transcriptional activity. J Biol Chem 282(15):11221–11229CrossRef
149.
Zurück zum Zitat Goo L, Tatiana G, Elizabeth M, Ramanarao D, Pal SA, Brown Jeffrey B, Randal M, Yang G–Y, William RJ, Mark EB (2010) Phosphoinositide 3-kinase signaling mediates β-catenin activation in intestinal epithelial stem and progenitor cells in colitis. Gastroenterology 139(3):869–881. e869CrossRef Goo L, Tatiana G, Elizabeth M, Ramanarao D, Pal SA, Brown Jeffrey B, Randal M, Yang G–Y, William RJ, Mark EB (2010) Phosphoinositide 3-kinase signaling mediates β-catenin activation in intestinal epithelial stem and progenitor cells in colitis. Gastroenterology 139(3):869–881. e869CrossRef
150.
Zurück zum Zitat Sho-ichi Y, Takanori M (2010) Advanced glycation end products, oxidative stress and diabetic nephropathy. Oxid Med Cell Longev 3(2):101–108CrossRef Sho-ichi Y, Takanori M (2010) Advanced glycation end products, oxidative stress and diabetic nephropathy. Oxid Med Cell Longev 3(2):101–108CrossRef
153.
Zurück zum Zitat Xiang H, Yong C (2013) Possible participation of receptor for advanced glycation end products (RAGE) in the origin of cancer stem cells in diabetic patients with colon cancer. Med Hypotheses 80(5):620–623CrossRef Xiang H, Yong C (2013) Possible participation of receptor for advanced glycation end products (RAGE) in the origin of cancer stem cells in diabetic patients with colon cancer. Med Hypotheses 80(5):620–623CrossRef
154.
Zurück zum Zitat Jeong-Hun K (2014). Protein kinase C (PKC) isozymes and cancer. New J Sci 2014 Jeong-Hun K (2014). Protein kinase C (PKC) isozymes and cancer. New J Sci 2014 
156.
Zurück zum Zitat Polina G, Alexander K, Nataliya B, Melania T, Isabelle P, Arnon N, Izhar H, Tsvee L (2006) cAMP-induced PKCζ activation increases functional CXCR4 expression on human CD34+ hematopoietic progenitors. Blood 107(3):870–879 Polina G, Alexander K, Nataliya B, Melania T, Isabelle P, Arnon N, Izhar H, Tsvee L (2006) cAMP-induced PKCζ activation increases functional CXCR4 expression on human CD34+ hematopoietic progenitors. Blood 107(3):870–879
157.
Zurück zum Zitat Suryatheja A, Abhilasha S, Mohamed EG, Simran B, Marshall Jr Gailen D, Gardner Lauren H, Yoshiko S, ElShamy Wael M (2016) Geminin overexpression-dependent recruitment and crosstalk with mesenchymal stem cells enhance aggressiveness in triple negative breast cancers. Oncotarget 7(15):20869 Suryatheja A, Abhilasha S, Mohamed EG, Simran B, Marshall Jr Gailen D, Gardner Lauren H, Yoshiko S, ElShamy Wael M (2016) Geminin overexpression-dependent recruitment and crosstalk with mesenchymal stem cells enhance aggressiveness in triple negative breast cancers. Oncotarget 7(15):20869
158.
Zurück zum Zitat Rihua Z, Xiaolin P, Huang Zuhu WGF, Guoxin Z (2011) Osteopontin enhances the expression and activity of MMP-2 via the SDF-1/CXCR4 axis in hepatocellular carcinoma cell lines. PLoS One 6(8):e23831CrossRef Rihua Z, Xiaolin P, Huang Zuhu WGF, Guoxin Z (2011) Osteopontin enhances the expression and activity of MMP-2 via the SDF-1/CXCR4 axis in hepatocellular carcinoma cell lines. PLoS One 6(8):e23831CrossRef
159.
Zurück zum Zitat Das Shamik SRS, Shevde Lalita A (2011) Hedgehog signaling induced by breast cancer cells promotes osteoclastogenesis and osteolysis. J Biol Chem 286(11):9612–9622PubMedCrossRef Das Shamik SRS, Shevde Lalita A (2011) Hedgehog signaling induced by breast cancer cells promotes osteoclastogenesis and osteolysis. J Biol Chem 286(11):9612–9622PubMedCrossRef
160.
Zurück zum Zitat Matteo P, Paola C (2010) Rac and rho GTPases in cancer cell motility control. Cell Commun Signal 8(1):23CrossRef Matteo P, Paola C (2010) Rac and rho GTPases in cancer cell motility control. Cell Commun Signal 8(1):23CrossRef
161.
Zurück zum Zitat Schiraldi M, Raucci A, Munoz LM, Livoti E, Celona B, Venereau E, Apuzzo T, De Marchis F, Pedotti M, Bachi A, Thelen M, Varani L, Mellado M, Proudfoot A, Bianchi ME, Uguccioni M (2012) HMGB1 promotes recruitment of inflammatory cells to damaged tissues by forming a complex with CXCL12 and signaling via CXCR4. J Exp Med 209(3):551–563. https://doi.org/10.1084/jem.20111739 PubMedPubMedCentralCrossRef Schiraldi M, Raucci A, Munoz LM, Livoti E, Celona B, Venereau E, Apuzzo T, De Marchis F, Pedotti M, Bachi A, Thelen M, Varani L, Mellado M, Proudfoot A, Bianchi ME, Uguccioni M (2012) HMGB1 promotes recruitment of inflammatory cells to damaged tissues by forming a complex with CXCL12 and signaling via CXCR4. J Exp Med 209(3):551–563. https://​doi.​org/​10.​1084/​jem.​20111739 PubMedPubMedCentralCrossRef
162.
Zurück zum Zitat Katrin K, Günter F (2013) RAGE regulation and signaling in inflammation and beyond. J Leukoc Biol 94(1):55–68CrossRef Katrin K, Günter F (2013) RAGE regulation and signaling in inflammation and beyond. J Leukoc Biol 94(1):55–68CrossRef
163.
Zurück zum Zitat Sabine H-K, Suchitra N, Thatchawan T, Manoj M, Alok P, Saeid G, Thomas K (2014) Mechanisms of therapeutic resistance in cancer (stem) cells with emphasis on thyroid cancer cells. Front Endocrinol 5:37 Sabine H-K, Suchitra N, Thatchawan T, Manoj M, Alok P, Saeid G, Thomas K (2014) Mechanisms of therapeutic resistance in cancer (stem) cells with emphasis on thyroid cancer cells. Front Endocrinol 5:37
164.
Zurück zum Zitat Laura C, Stefania L, Maddalena A, Roberta A, Enrico R, Daniela C, Calogero Raffaele A, Federica C (2013) The noninflammatory role of high mobility group box 1/Toll-like receptor 2 axis in the self-renewal of mammary cancer stem cells. The FASEB Journal 27(12):4731–4744CrossRef Laura C, Stefania L, Maddalena A, Roberta A, Enrico R, Daniela C, Calogero Raffaele A, Federica C (2013) The noninflammatory role of high mobility group box 1/Toll-like receptor 2 axis in the self-renewal of mammary cancer stem cells. The FASEB Journal 27(12):4731–4744CrossRef
165.
Zurück zum Zitat Aparna J, Bijay D, Steel Jason C (2016) Epithelial-to-mesenchymal plasticity of cancer stem cells: therapeutic targets in hepatocellular carcinoma. J Hematol Oncol 9(1):74CrossRef Aparna J, Bijay D, Steel Jason C (2016) Epithelial-to-mesenchymal plasticity of cancer stem cells: therapeutic targets in hepatocellular carcinoma. J Hematol Oncol 9(1):74CrossRef
166.
Zurück zum Zitat Takanobu T, Tadashi U, Akiko S-S, Masayoshi T (2017) Generation of glyceraldehyde-derived advanced glycation end-products in pancreatic cancer cells and the potential of tumor promotion. World J Gastroenterol 23(27):4910CrossRef Takanobu T, Tadashi U, Akiko S-S, Masayoshi T (2017) Generation of glyceraldehyde-derived advanced glycation end-products in pancreatic cancer cells and the potential of tumor promotion. World J Gastroenterol 23(27):4910CrossRef
167.
Zurück zum Zitat Masayo M, Hidenori K, Yoshiko O, Tomoaki M, Katsuhito M, Takuhito S, Yohei M, Koka M, Shinya F, Atsushi S (2013) Receptor for advanced glycation end products regulates adipocyte hypertrophy and insulin sensitivity in mice: involvement of Toll-like receptor 2. Diabetes 62(2):478–489CrossRef Masayo M, Hidenori K, Yoshiko O, Tomoaki M, Katsuhito M, Takuhito S, Yohei M, Koka M, Shinya F, Atsushi S (2013) Receptor for advanced glycation end products regulates adipocyte hypertrophy and insulin sensitivity in mice: involvement of Toll-like receptor 2. Diabetes 62(2):478–489CrossRef
168.
Zurück zum Zitat Xiaolong M, Jie Z, Shuying L, Mollianne M, Gonzalez-Angulo AM (2012) A new hypothesis for the cancer mechanism. Cancer Metastasis Rev 31(1–2):247–268 Xiaolong M, Jie Z, Shuying L, Mollianne M, Gonzalez-Angulo AM (2012) A new hypothesis for the cancer mechanism. Cancer Metastasis Rev 31(1–2):247–268
171.
172.
Zurück zum Zitat Joseph M, MacKerell Alexander D, Weber David J (2007) A search for inhibitors of S100B, a member of the S100 family of calcium-binding proteins. Mini Rev Med Chem 7(6):609–616CrossRef Joseph M, MacKerell Alexander D, Weber David J (2007) A search for inhibitors of S100B, a member of the S100 family of calcium-binding proteins. Mini Rev Med Chem 7(6):609–616CrossRef
173.
Zurück zum Zitat Amlanjyoti D, Shampa M, Piya G, Atanu M, Israr A, Seemana B, Tapashi M, Asit M, Koushik R, Sandeep S (2014) Simultaneous inhibition of key growth pathways in melanoma cells and tumor regression by a designed bidentate constrained helical peptide. Pept Sci 102(4):344–358CrossRef Amlanjyoti D, Shampa M, Piya G, Atanu M, Israr A, Seemana B, Tapashi M, Asit M, Koushik R, Sandeep S (2014) Simultaneous inhibition of key growth pathways in melanoma cells and tumor regression by a designed bidentate constrained helical peptide. Pept Sci 102(4):344–358CrossRef
174.
Zurück zum Zitat Björk P, Björk A, Vogl T, Stenström M, Liberg D, Olsson A, Roth J, Ivars F, Leanderson T (2009) Identification of human S100A9 as a novel target for treatment of autoimmune disease via binding to quinoline-3-carboxamides. PLoS Biol 7(4):e1000097PubMedCentralCrossRef Björk P, Björk A, Vogl T, Stenström M, Liberg D, Olsson A, Roth J, Ivars F, Leanderson T (2009) Identification of human S100A9 as a novel target for treatment of autoimmune disease via binding to quinoline-3-carboxamides. PLoS Biol 7(4):e1000097PubMedCentralCrossRef
175.
Zurück zum Zitat Pili R, Häggman M, Stadler WM, Gingrich JR, Assikis VJ, Björk A, Nordle Ö, Forsberg G, Carducci MA, Armstrong AJ (2011) Phase II randomized, double-blind, placebo-controlled study of tasquinimod in men with minimally symptomatic metastatic castrate-resistant prostate cancer. J Clin Oncol 29(30):4022–4028PubMedCrossRef Pili R, Häggman M, Stadler WM, Gingrich JR, Assikis VJ, Björk A, Nordle Ö, Forsberg G, Carducci MA, Armstrong AJ (2011) Phase II randomized, double-blind, placebo-controlled study of tasquinimod in men with minimally symptomatic metastatic castrate-resistant prostate cancer. J Clin Oncol 29(30):4022–4028PubMedCrossRef
176.
Zurück zum Zitat Hong Q, Beatrisa L, Ippei S, Guowei W, Cha Soungchul C, Rao Sheetal S, Jianfei Q, Yared H, Nurieva Roza DKC (2014) Generation of a new therapeutic peptide that depletes myeloid-derived suppressor cells in tumor-bearing mice. Nat Med 20(6):676–681CrossRef Hong Q, Beatrisa L, Ippei S, Guowei W, Cha Soungchul C, Rao Sheetal S, Jianfei Q, Yared H, Nurieva Roza DKC (2014) Generation of a new therapeutic peptide that depletes myeloid-derived suppressor cells in tumor-bearing mice. Nat Med 20(6):676–681CrossRef
177.
Zurück zum Zitat Limin Z, Haowen J, Gang X, Hui W, Bin G, Jun L, Shanghua M, Rong N, Yan J, Qiang D (2015) Proteins S100A8 and S100A9 are potential biomarkers for renal cell carcinoma in the early stages: results from a proteomic study integrated with bioinformatics analysis. Mol Med Rep 11(6):4093–4100CrossRef Limin Z, Haowen J, Gang X, Hui W, Bin G, Jun L, Shanghua M, Rong N, Yan J, Qiang D (2015) Proteins S100A8 and S100A9 are potential biomarkers for renal cell carcinoma in the early stages: results from a proteomic study integrated with bioinformatics analysis. Mol Med Rep 11(6):4093–4100CrossRef
178.
Zurück zum Zitat Filip P, Tomasz R, Yuzhu C, Tatjana C-J (2016) The life and works of S100P-from conception to cancer. Am J Cancer Res 6(2):562 Filip P, Tomasz R, Yuzhu C, Tatjana C-J (2016) The life and works of S100P-from conception to cancer. Am J Cancer Res 6(2):562
179.
Zurück zum Zitat Thiruvengadam A, Vijaya R, Duoli S, Zhenghong P, Pal Ashutosh MDS, Bornmann William G, Logsdon Craig D (2013) Designing and developing S100P inhibitor 5-methyl cromolyn for pancreatic cancer therapy. Mol Cancer Ther 12(5):654–662CrossRef Thiruvengadam A, Vijaya R, Duoli S, Zhenghong P, Pal Ashutosh MDS, Bornmann William G, Logsdon Craig D (2013) Designing and developing S100P inhibitor 5-methyl cromolyn for pancreatic cancer therapy. Mol Cancer Ther 12(5):654–662CrossRef
181.
Zurück zum Zitat Yuki K, Yoichi T, Tomoe K, Kouji K, Takahiko I, Tomoko H, Ichiaki I, Michiteru Y, Kengo S, Fumio S (2013) Identification and characterization of the direct interaction between methotrexate (MTX) and high-mobility group box 1 (HMGB1) protein. PLoS One 8(5):e63073CrossRef Yuki K, Yoichi T, Tomoe K, Kouji K, Takahiko I, Tomoko H, Ichiaki I, Michiteru Y, Kengo S, Fumio S (2013) Identification and characterization of the direct interaction between methotrexate (MTX) and high-mobility group box 1 (HMGB1) protein. PLoS One 8(5):e63073CrossRef
182.
Zurück zum Zitat Takanori M, Sho-ichi Y, Masayoshi T, Seiji U, Kei F, Seiya O (2010) Nifedipine inhibits advanced glycation end products (AGEs) and their receptor (RAGE) interaction-mediated proximal tubular cell injury via peroxisome proliferator-activated receptor-gamma activation. Biochem Biophys Res Commun 398(2):326–330CrossRef Takanori M, Sho-ichi Y, Masayoshi T, Seiji U, Kei F, Seiya O (2010) Nifedipine inhibits advanced glycation end products (AGEs) and their receptor (RAGE) interaction-mediated proximal tubular cell injury via peroxisome proliferator-activated receptor-gamma activation. Biochem Biophys Res Commun 398(2):326–330CrossRef
183.
Zurück zum Zitat Jie C, Xiaoyan L, Jie Z, Yueran Z (2012) Targeting HMGB1 inhibits ovarian cancer growth and metastasis by lentivirus-mediated RNA interference. J Cell Physiol 227(11):3629–3638CrossRef Jie C, Xiaoyan L, Jie Z, Yueran Z (2012) Targeting HMGB1 inhibits ovarian cancer growth and metastasis by lentivirus-mediated RNA interference. J Cell Physiol 227(11):3629–3638CrossRef
184.
Zurück zum Zitat Dong Y-D, Cui L, Peng C-H, Cheng D-F, Han B-S, Fang H (2013) Expression and clinical significance of HMGB1 in human liver cancer: knockdown inhibits tumor growth and metastasis in vitro and in vivo. Oncol Rep 29(1):87–94PubMedCrossRef Dong Y-D, Cui L, Peng C-H, Cheng D-F, Han B-S, Fang H (2013) Expression and clinical significance of HMGB1 in human liver cancer: knockdown inhibits tumor growth and metastasis in vitro and in vivo. Oncol Rep 29(1):87–94PubMedCrossRef
185.
Zurück zum Zitat Huang Z, Zhong Z, Zhang L, Wang X, Xu R, Zhu L, Wang Z, Hu S, Zhao X (2015) Down-regulation of HMGB1 expression by shRNA constructs inhibits the bioactivity of urothelial carcinoma cell lines via the NF-κB pathway. Sci Rep 5 Huang Z, Zhong Z, Zhang L, Wang X, Xu R, Zhu L, Wang Z, Hu S, Zhao X (2015) Down-regulation of HMGB1 expression by shRNA constructs inhibits the bioactivity of urothelial carcinoma cell lines via the NF-κB pathway. Sci Rep 5
186.
Zurück zum Zitat Laura P, Xue J, David L, Sandra P, Sandro J, Forest Kelly H, Saad-Jube Zeyana S, Napolitano A, Pagano I, Negi VS (2017) HMGB1 targeting by ethyl pyruvate suppresses malignant phenotype of human mesothelioma. Oncotarget 8(14):22649CrossRef Laura P, Xue J, David L, Sandra P, Sandro J, Forest Kelly H, Saad-Jube Zeyana S, Napolitano A, Pagano I, Negi VS (2017) HMGB1 targeting by ethyl pyruvate suppresses malignant phenotype of human mesothelioma. Oncotarget 8(14):22649CrossRef
187.
Zurück zum Zitat Li ML, Wang XF, Tan ZJ, Dong P, Gu J, Lu JH, Wu XS, Zhang L, Ding QC, Wu WG (2012) Ethyl pyruvate administration suppresses growth and invasion of gallbladder cancer cells via downregulation of HMGB1-RAGE axis. Int J Immunopathol Pharmacol 25(4):955–965PubMedCrossRef Li ML, Wang XF, Tan ZJ, Dong P, Gu J, Lu JH, Wu XS, Zhang L, Ding QC, Wu WG (2012) Ethyl pyruvate administration suppresses growth and invasion of gallbladder cancer cells via downregulation of HMGB1-RAGE axis. Int J Immunopathol Pharmacol 25(4):955–965PubMedCrossRef
188.
Zurück zum Zitat Shen M, Lu J, Dai W, Wang F, Xu L, Chen K, He L, Cheng P, Zhang Y, Wang C (2013) Ethyl pyruvate ameliorates hepatic ischemia-reperfusion injury by inhibiting intrinsic pathway of apoptosis and autophagy. Mediat Inflamm 2013 Shen M, Lu J, Dai W, Wang F, Xu L, Chen K, He L, Cheng P, Zhang Y, Wang C (2013) Ethyl pyruvate ameliorates hepatic ischemia-reperfusion injury by inhibiting intrinsic pathway of apoptosis and autophagy. Mediat Inflamm 2013
189.
Zurück zum Zitat Du G-J, Zhiyu Z, Xiao-Dong W, Yu C, Tyler C, Chun-Su Y, Wang C-Z (2012) Epigallocatechin Gallate (EGCG) is the most effective cancer chemopreventive polyphenol in green tea. Nutrients 4(11):1679–1691PubMedPubMedCentralCrossRef Du G-J, Zhiyu Z, Xiao-Dong W, Yu C, Tyler C, Chun-Su Y, Wang C-Z (2012) Epigallocatechin Gallate (EGCG) is the most effective cancer chemopreventive polyphenol in green tea. Nutrients 4(11):1679–1691PubMedPubMedCentralCrossRef
190.
191.
Zurück zum Zitat Li W, Ashok M, Li J, Yang H, Sama AE, Wang H (2007) A major ingredient of green tea rescues mice from lethal sepsis partly by inhibiting HMGB1. PLoS One 2(11):e1153PubMedPubMedCentralCrossRef Li W, Ashok M, Li J, Yang H, Sama AE, Wang H (2007) A major ingredient of green tea rescues mice from lethal sepsis partly by inhibiting HMGB1. PLoS One 2(11):e1153PubMedPubMedCentralCrossRef
192.
Zurück zum Zitat Mollica L, De Marchis F, Spitaleri A, Dallacosta C, Pennacchini D, Zamai M, Agresti A, Trisciuoglio L, Musco G, Bianchi ME (2007) Glycyrrhizin binds to high-mobility group box 1 protein and inhibits its cytokine activities. Chem Biol 14(4):431–441PubMedCrossRef Mollica L, De Marchis F, Spitaleri A, Dallacosta C, Pennacchini D, Zamai M, Agresti A, Trisciuoglio L, Musco G, Bianchi ME (2007) Glycyrrhizin binds to high-mobility group box 1 protein and inhibits its cytokine activities. Chem Biol 14(4):431–441PubMedCrossRef
193.
Zurück zum Zitat Smolarczyk R, Cichoń T, Matuszczak S, Mitrus I, Lesiak M, Kobusińska M, Kamysz W, Jarosz M, Sieroń A, Szalak S (2012) The role of glycyrrhizin, an inhibitor of HMGB1 protein, in anticancer therapy. Archivum Immunologiae Et Therapiae Experimentalis 60(5):391–399PubMedCrossRef Smolarczyk R, Cichoń T, Matuszczak S, Mitrus I, Lesiak M, Kobusińska M, Kamysz W, Jarosz M, Sieroń A, Szalak S (2012) The role of glycyrrhizin, an inhibitor of HMGB1 protein, in anticancer therapy. Archivum Immunologiae Et Therapiae Experimentalis 60(5):391–399PubMedCrossRef
194.
Zurück zum Zitat Dhumale SS, Waghela BN, Pathak C (2015) Quercetin protects necrotic insult and promotes apoptosis by attenuating the expression of RAGE and its ligand HMGB1 in human breast adenocarcinoma cells. IUBMB Life 67(5):361–373PubMedCrossRef Dhumale SS, Waghela BN, Pathak C (2015) Quercetin protects necrotic insult and promotes apoptosis by attenuating the expression of RAGE and its ligand HMGB1 in human breast adenocarcinoma cells. IUBMB Life 67(5):361–373PubMedCrossRef
195.
Zurück zum Zitat Julius A, Hopper W (2017) Inhibition of advanced glycation end-product formation by quercetin and catechin: an alternative therapy for treating diabetic complications. Asian J Pharm Clin Res 10(11):173–176CrossRef Julius A, Hopper W (2017) Inhibition of advanced glycation end-product formation by quercetin and catechin: an alternative therapy for treating diabetic complications. Asian J Pharm Clin Res 10(11):173–176CrossRef
196.
Zurück zum Zitat Tang Y, Chen A (2014) Curcumin eliminates the effect of advanced glycation end-products (AGEs) on the divergent regulation of gene expression of receptors of AGEs by interrupting leptin signaling. Lab Investig 94(5):503–516PubMedCrossRef Tang Y, Chen A (2014) Curcumin eliminates the effect of advanced glycation end-products (AGEs) on the divergent regulation of gene expression of receptors of AGEs by interrupting leptin signaling. Lab Investig 94(5):503–516PubMedCrossRef
197.
Zurück zum Zitat Lin J, Tang Y, Kang Q, Feng Y, Chen A (2012) Curcumin inhibits gene expression of receptor for advanced glycation end-products (RAGE) in hepatic stellate cells in vitro by elevating PPARγ activity and attenuating oxidative stress. Br J Pharmacol 166(8):2212–2227PubMedPubMedCentralCrossRef Lin J, Tang Y, Kang Q, Feng Y, Chen A (2012) Curcumin inhibits gene expression of receptor for advanced glycation end-products (RAGE) in hepatic stellate cells in vitro by elevating PPARγ activity and attenuating oxidative stress. Br J Pharmacol 166(8):2212–2227PubMedPubMedCentralCrossRef
198.
Zurück zum Zitat Wang C, Nie H, Li K, Zhang Y-x, Yang F, Li C-b, Wang C-f, Gong Q (2012) Curcumin inhibits HMGB1 releasing and attenuates concanavalin A-induced hepatitis in mice. Eur J Pharmacol 697(1):152–157PubMedCrossRef Wang C, Nie H, Li K, Zhang Y-x, Yang F, Li C-b, Wang C-f, Gong Q (2012) Curcumin inhibits HMGB1 releasing and attenuates concanavalin A-induced hepatitis in mice. Eur J Pharmacol 697(1):152–157PubMedCrossRef
199.
Zurück zum Zitat Kim D-C, Lee W, Bae J-S (2011) Vascular anti-inflammatory effects of curcumin on HMGB1-mediated responses in vitro. Inflamm Res 60(12):1161–1168PubMedCrossRef Kim D-C, Lee W, Bae J-S (2011) Vascular anti-inflammatory effects of curcumin on HMGB1-mediated responses in vitro. Inflamm Res 60(12):1161–1168PubMedCrossRef
200.
Zurück zum Zitat Vinod BS, Antony J, Nair HH, Puliyappadamba VT, Saikia M, Narayanan SS, Bevin A, Anto RJ (2013) Mechanistic evaluation of the signaling events regulating curcumin-mediated chemosensitization of breast cancer cells to 5-fluorouracil. Cell Death Dis 4(2):e505PubMedPubMedCentralCrossRef Vinod BS, Antony J, Nair HH, Puliyappadamba VT, Saikia M, Narayanan SS, Bevin A, Anto RJ (2013) Mechanistic evaluation of the signaling events regulating curcumin-mediated chemosensitization of breast cancer cells to 5-fluorouracil. Cell Death Dis 4(2):e505PubMedPubMedCentralCrossRef
201.
202.
Zurück zum Zitat Mizumoto S, Takahashi J, Kazuyuki S (2012) Receptor for advanced glycation end products (RAGE) functions as receptor for specific sulfated glycosaminoglycans, and anti-RAGE antibody or sulfated glycosaminoglycans delivered in vivo inhibit pulmonary metastasis of tumor cells. J Biol Chem 287(23):18985–18994PubMedPubMedCentralCrossRef Mizumoto S, Takahashi J, Kazuyuki S (2012) Receptor for advanced glycation end products (RAGE) functions as receptor for specific sulfated glycosaminoglycans, and anti-RAGE antibody or sulfated glycosaminoglycans delivered in vivo inhibit pulmonary metastasis of tumor cells. J Biol Chem 287(23):18985–18994PubMedPubMedCentralCrossRef
203.
Zurück zum Zitat Bongarzone S, Savickas V, Luzi F, Gee AD (2017) Targeting the receptor for advanced glycation endproducts (RAGE): a medicinal chemistry perspective. J Med Chem Bongarzone S, Savickas V, Luzi F, Gee AD (2017) Targeting the receptor for advanced glycation endproducts (RAGE): a medicinal chemistry perspective. J Med Chem
204.
Zurück zum Zitat Arumugam T, Ramachandran V, Gomez SB, Schmidt Ann M, Logsdon CD (2012) S100P-derived RAGE antagonistic peptide reduces tumor growth and metastasis. Clin Cancer Res 18(16):4356–4364PubMedCrossRef Arumugam T, Ramachandran V, Gomez SB, Schmidt Ann M, Logsdon CD (2012) S100P-derived RAGE antagonistic peptide reduces tumor growth and metastasis. Clin Cancer Res 18(16):4356–4364PubMedCrossRef
206.
Zurück zum Zitat Nakamura K, Yamagishi S-i, Nakamura Y, Takenaka K, Matsui T, Jinnouchi Y, Imaizumi T (2005) Telmisartan inhibits expression of a receptor for advanced glycation end products (RAGE) in angiotensin-II-exposed endothelial cells and decreases serum levels of soluble RAGE in patients with essential hypertension. Microvasc Res 70(3):137–141PubMedCrossRef Nakamura K, Yamagishi S-i, Nakamura Y, Takenaka K, Matsui T, Jinnouchi Y, Imaizumi T (2005) Telmisartan inhibits expression of a receptor for advanced glycation end products (RAGE) in angiotensin-II-exposed endothelial cells and decreases serum levels of soluble RAGE in patients with essential hypertension. Microvasc Res 70(3):137–141PubMedCrossRef
207.
Zurück zum Zitat Chen X-F, Zou J-J, Tang W, Lin W-D, Sun L-L, Bao Y, Chen H-Y, Zhang B, Ye F, Liu Z-M (2016) Metformin corrects RAGE overexpression caused signaling dysregulation and NF-κB targeted gene change. Int J Clin Exp Med 9(2):2913–2920 Chen X-F, Zou J-J, Tang W, Lin W-D, Sun L-L, Bao Y, Chen H-Y, Zhang B, Ye F, Liu Z-M (2016) Metformin corrects RAGE overexpression caused signaling dysregulation and NF-κB targeted gene change. Int J Clin Exp Med 9(2):2913–2920
208.
Zurück zum Zitat Kumar AA, Hayati ON, Subramani P, Urmila B (2017) Curcumin: the spicy modulator of breast carcinogenesis. J Exp Clin Cancer Res 36(1):98CrossRef Kumar AA, Hayati ON, Subramani P, Urmila B (2017) Curcumin: the spicy modulator of breast carcinogenesis. J Exp Clin Cancer Res 36(1):98CrossRef
209.
Zurück zum Zitat Zhang G, Xue Y-m, GAO F, Zhu B (2010) AGE-RAGE interaction promotes the proliferation of human colon carcinoma SW-480 cells [J]. Journal of Medical Postgraduates 9:008 Zhang G, Xue Y-m, GAO F, Zhu B (2010) AGE-RAGE interaction promotes the proliferation of human colon carcinoma SW-480 cells [J]. Journal of Medical Postgraduates 9:008
210.
Zurück zum Zitat Sun YP, Gu JF, Tan X, Bin WCF, Jia XB, Feng L, Liu JP (2016) Curcumin inhibits advanced glycation end product-induced oxidative stress and inflammatory responses in endothelial cell damage via trapping methylglyoxal. Mol Med Rep 13(2):1475–1486PubMedCrossRef Sun YP, Gu JF, Tan X, Bin WCF, Jia XB, Feng L, Liu JP (2016) Curcumin inhibits advanced glycation end product-induced oxidative stress and inflammatory responses in endothelial cell damage via trapping methylglyoxal. Mol Med Rep 13(2):1475–1486PubMedCrossRef
211.
Zurück zum Zitat Shen Y, Xu Z, Sheng Z (2017) Ability of resveratrol to inhibit advanced glycation end product formation and carbohydrate-hydrolyzing enzyme activity and to conjugate methylglyoxal. Food Chem 216:153–160PubMedCrossRef Shen Y, Xu Z, Sheng Z (2017) Ability of resveratrol to inhibit advanced glycation end product formation and carbohydrate-hydrolyzing enzyme activity and to conjugate methylglyoxal. Food Chem 216:153–160PubMedCrossRef
212.
Zurück zum Zitat Moridi H, Karimi J, Sheikh N, Goodarzi MT, Saidijam M, Yadegarazari R, Khazaei M, Khodadadi I, Tavilani H, Piri H (2015) Resveratrol-dependent down-regulation of receptor for advanced glycation end-products and oxidative stress in kidney of rats with diabetes. Int J Endocrinol Metab 13(2) Moridi H, Karimi J, Sheikh N, Goodarzi MT, Saidijam M, Yadegarazari R, Khazaei M, Khodadadi I, Tavilani H, Piri H (2015) Resveratrol-dependent down-regulation of receptor for advanced glycation end-products and oxidative stress in kidney of rats with diabetes. Int J Endocrinol Metab 13(2)
213.
Zurück zum Zitat Singh CK, Ndiaye MA, Ahmad N (2015) Resveratrol and cancer: challenges for clinical translation. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease 1852(6):1178–1185CrossRef Singh CK, Ndiaye MA, Ahmad N (2015) Resveratrol and cancer: challenges for clinical translation. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease 1852(6):1178–1185CrossRef
214.
Zurück zum Zitat Lv L, Shao X, Chen H, Ho C-T, Sang S (2011) Genistein inhibits advanced glycation end product formation by trapping methylglyoxal. Chem Res Toxicol 24(4):579–586PubMedCrossRef Lv L, Shao X, Chen H, Ho C-T, Sang S (2011) Genistein inhibits advanced glycation end product formation by trapping methylglyoxal. Chem Res Toxicol 24(4):579–586PubMedCrossRef
215.
Zurück zum Zitat Russo M, Russo GL, Daglia M, Kasi PD, Ravi S, Nabavi SF, Nabavi SM (2016) Understanding genistein in cancer: the “good” and the “bad” effects: a review. Food Chem 196:589–600PubMedCrossRef Russo M, Russo GL, Daglia M, Kasi PD, Ravi S, Nabavi SF, Nabavi SM (2016) Understanding genistein in cancer: the “good” and the “bad” effects: a review. Food Chem 196:589–600PubMedCrossRef
216.
Zurück zum Zitat Saadat Nadia, Gupta Smiti V (2012). Potential role of garcinol as an anticancer agent. J Oncol 2012 Saadat Nadia, Gupta Smiti V (2012). Potential role of garcinol as an anticancer agent. J Oncol 2012
217.
Zurück zum Zitat Fumio Y, Toshiaki A, Yoshihiro Y, Hiroyuki N (2000) Antioxidative and anti-glycation activity of garcinol from Garcinia indica fruit rind. J Agric Food Chem 48(2):180–185CrossRef Fumio Y, Toshiaki A, Yoshihiro Y, Hiroyuki N (2000) Antioxidative and anti-glycation activity of garcinol from Garcinia indica fruit rind. J Agric Food Chem 48(2):180–185CrossRef
221.
Zurück zum Zitat Gu H, Yang L, Sun Q, Zhou B, Tang N, Cong R, Zeng Y, Wang B (2008) Gly82Ser polymorphism of the receptor for advanced glycation end products is associated with an increased risk of gastric cancer in a Chinese population. Clin Cancer Res 14(11):3627–3632PubMedCrossRef Gu H, Yang L, Sun Q, Zhou B, Tang N, Cong R, Zeng Y, Wang B (2008) Gly82Ser polymorphism of the receptor for advanced glycation end products is associated with an increased risk of gastric cancer in a Chinese population. Clin Cancer Res 14(11):3627–3632PubMedCrossRef
222.
Zurück zum Zitat Park SJ, Kleffmann T, Hessian PA (2011) The G82S polymorphism promotes glycosylation of the receptor for advanced glycation end products (RAGE) at asparagine 81 comparison of wild-type rage with the g82s polymorphic variant. J Biol Chem 286(24):21384–21392PubMedPubMedCentralCrossRef Park SJ, Kleffmann T, Hessian PA (2011) The G82S polymorphism promotes glycosylation of the receptor for advanced glycation end products (RAGE) at asparagine 81 comparison of wild-type rage with the g82s polymorphic variant. J Biol Chem 286(24):21384–21392PubMedPubMedCentralCrossRef
223.
Zurück zum Zitat Wang X, Cui E, Zeng H, Hua F, Wang B, Mao W, Feng X (2012) RAGE genetic polymorphisms are associated with risk, chemotherapy response and prognosis in patients with advanced NSCLC. PLoS One 7(10):–e43734 Wang X, Cui E, Zeng H, Hua F, Wang B, Mao W, Feng X (2012) RAGE genetic polymorphisms are associated with risk, chemotherapy response and prognosis in patients with advanced NSCLC. PLoS One 7(10):–e43734
224.
Zurück zum Zitat Pan Hongming, He Lan, Wang Bin, Niu Wenquan. 2014. The relationship between RAGE gene four common polymorphisms and breast cancer risk in northeastern Han Chinese. Sci Rep 4 Pan Hongming, He Lan, Wang Bin, Niu Wenquan. 2014. The relationship between RAGE gene four common polymorphisms and breast cancer risk in northeastern Han Chinese. Sci Rep 4
225.
Zurück zum Zitat Qian F, Sun BL, Zhang WY, Ke J, Zhu J (2014) Gly82Ser polymorphism of the receptor for advanced glycation end-product (RAGE) potential high risk in patients with colorectal cancer. Tumor Biol 35(4):3171–3175CrossRef Qian F, Sun BL, Zhang WY, Ke J, Zhu J (2014) Gly82Ser polymorphism of the receptor for advanced glycation end-product (RAGE) potential high risk in patients with colorectal cancer. Tumor Biol 35(4):3171–3175CrossRef
226.
Zurück zum Zitat Su SC, Hsieh MJ, Chou YE, Fan WL, Yeh CB, Yang SF (2015) Effects of RAGE gene polymorphisms on the risk and progression of hepatocellular carcinoma. Medicine 94(34):e1396PubMedPubMedCentralCrossRef Su SC, Hsieh MJ, Chou YE, Fan WL, Yeh CB, Yang SF (2015) Effects of RAGE gene polymorphisms on the risk and progression of hepatocellular carcinoma. Medicine 94(34):e1396PubMedPubMedCentralCrossRef
227.
Zurück zum Zitat Su S, Chien M, Lin C, Chen M, Yang S (2015) RAGE gene polymorphism and environmental factor in the risk of oral cancer. J Dent Res 94(3):403–411PubMedPubMedCentralCrossRef Su S, Chien M, Lin C, Chen M, Yang S (2015) RAGE gene polymorphism and environmental factor in the risk of oral cancer. J Dent Res 94(3):403–411PubMedPubMedCentralCrossRef
228.
Zurück zum Zitat Xia W, Xu Y, Mao Q, Dong G, Shi R, Wang J, Zheng Y, Xu L, Jiang F (2015) Association of RAGE polymorphisms and cancer risk: a meta-analysis of 27 studies. Med Oncol 32(2):33CrossRef Xia W, Xu Y, Mao Q, Dong G, Shi R, Wang J, Zheng Y, Xu L, Jiang F (2015) Association of RAGE polymorphisms and cancer risk: a meta-analysis of 27 studies. Med Oncol 32(2):33CrossRef
229.
Zurück zum Zitat Zhao D-C, Lu H-W, Huang Z-H (2015) Association between the receptor for advanced glycation end products gene polymorphisms and cancer risk: a systematic review and meta-analysis. J buon 20:614–624PubMed Zhao D-C, Lu H-W, Huang Z-H (2015) Association between the receptor for advanced glycation end products gene polymorphisms and cancer risk: a systematic review and meta-analysis. J buon 20:614–624PubMed
230.
Zurück zum Zitat Liu S, Tong X, He M, Fu X, Zhang Y, Fan H (2016) The receptor for advanced glycation end products gene polymorphisms contribute to cancer susceptibility: evidence from meta-analysis. Int J Clin Exp Med 9(3):5867–5879 Liu S, Tong X, He M, Fu X, Zhang Y, Fan H (2016) The receptor for advanced glycation end products gene polymorphisms contribute to cancer susceptibility: evidence from meta-analysis. Int J Clin Exp Med 9(3):5867–5879
231.
Zurück zum Zitat Yue L, Zhang Q, He L, Zhang M, Dong J, Zhao D, Ma H, Pan H, Zheng L (2016) Genetic predisposition of six well-defined polymorphisms in HMGB1/RAGE pathway to breast cancer in a large Han Chinese population. J Cell Mol Med 20(10):1966–1973PubMedPubMedCentralCrossRef Yue L, Zhang Q, He L, Zhang M, Dong J, Zhao D, Ma H, Pan H, Zheng L (2016) Genetic predisposition of six well-defined polymorphisms in HMGB1/RAGE pathway to breast cancer in a large Han Chinese population. J Cell Mol Med 20(10):1966–1973PubMedPubMedCentralCrossRef
232.
Zurück zum Zitat Taijie L, Weijuan Q, Yanqiong L, Shan L, Xue Q, Zhiming L (2017) Effect of RAGE gene polymorphisms and circulating sRAGE levels on susceptibility to gastric cancer: a case–control study. Cancer Cell Int 17(1):19CrossRef Taijie L, Weijuan Q, Yanqiong L, Shan L, Xue Q, Zhiming L (2017) Effect of RAGE gene polymorphisms and circulating sRAGE levels on susceptibility to gastric cancer: a case–control study. Cancer Cell Int 17(1):19CrossRef
233.
Zurück zum Zitat Gaens KH, Ferreira I, van der Kallen Carla JH, van Greevenbroek Marleen MJ, Blaak Ellen E, Feskens Edith JM, Dekker Jacqueline M, Giel N, Heine Robert J, ‘t Hart Leen M (2009) Association of polymorphism in the receptor for advanced glycation end products (RAGE) gene with circulating RAGE levels. J Clin Endocrinol Metabol 94(12):5174–5180CrossRef Gaens KH, Ferreira I, van der Kallen Carla JH, van Greevenbroek Marleen MJ, Blaak Ellen E, Feskens Edith JM, Dekker Jacqueline M, Giel N, Heine Robert J, ‘t Hart Leen M (2009) Association of polymorphism in the receptor for advanced glycation end products (RAGE) gene with circulating RAGE levels. J Clin Endocrinol Metabol 94(12):5174–5180CrossRef
234.
Zurück zum Zitat Kalea AZ, Schmidt AM, Hudson BI (2009) RAGE: a novel biological and genetic marker for vascular disease. Clin Sci 116(8):621–637CrossRef Kalea AZ, Schmidt AM, Hudson BI (2009) RAGE: a novel biological and genetic marker for vascular disease. Clin Sci 116(8):621–637CrossRef
235.
Zurück zum Zitat Hofmann MA, Drury S, Hudson BI, Gleason MR, Qu W, Lu Y, Lalla E, Chitnis S, Monteiro J, Stickland MH (2002) RAGE and arthritis: the G82S polymorphism amplifies the inflammatory response. Genes Immun 3(3):123PubMedCrossRef Hofmann MA, Drury S, Hudson BI, Gleason MR, Qu W, Lu Y, Lalla E, Chitnis S, Monteiro J, Stickland MH (2002) RAGE and arthritis: the G82S polymorphism amplifies the inflammatory response. Genes Immun 3(3):123PubMedCrossRef
237.
Zurück zum Zitat Geroldi D, Falcone C, Minoretti P, Emanuele E, Arra M, D'angelo A (2006) High levels of soluble receptor for advanced glycation end products may be a marker of extreme longevity in humans. J Am Geriatr Soc 54(7):1149–1150PubMedCrossRef Geroldi D, Falcone C, Minoretti P, Emanuele E, Arra M, D'angelo A (2006) High levels of soluble receptor for advanced glycation end products may be a marker of extreme longevity in humans. J Am Geriatr Soc 54(7):1149–1150PubMedCrossRef
238.
Zurück zum Zitat Li S, Li T, Qin W, Qin X, Liu Y, Liu Z (2017) Effect of RAGE gene polymorphisms and circulating sRAGE levels on susceptibility to gastric cancer: a case–control study. Cancer Cell Int 17(1):19PubMedPubMedCentralCrossRef Li S, Li T, Qin W, Qin X, Liu Y, Liu Z (2017) Effect of RAGE gene polymorphisms and circulating sRAGE levels on susceptibility to gastric cancer: a case–control study. Cancer Cell Int 17(1):19PubMedPubMedCentralCrossRef
239.
Zurück zum Zitat Tomáš K, Marie J, Oto M, Aleš Ž, Tomáš Z, Marta K (2010) Soluble receptor for advanced glycation end-products (sRAGE) and polymorphisms of RAGE and glyoxalase I genes in patients with pancreas cancer. Clin Biochem 43(10–11):882–886 Tomáš K, Marie J, Oto M, Aleš Ž, Tomáš Z, Marta K (2010) Soluble receptor for advanced glycation end-products (sRAGE) and polymorphisms of RAGE and glyoxalase I genes in patients with pancreas cancer. Clin Biochem 43(10–11):882–886
240.
Zurück zum Zitat Jing R, Cui M, Wang J, Wang H (2010) Receptor for advanced glycation end products (RAGE) soluble form (sRAGE): a new biomarker for lung cancer. Neoplasma 57(1):55–61PubMedCrossRef Jing R, Cui M, Wang J, Wang H (2010) Receptor for advanced glycation end products (RAGE) soluble form (sRAGE): a new biomarker for lung cancer. Neoplasma 57(1):55–61PubMedCrossRef
242.
243.
Zurück zum Zitat Boor P, Celec P, Klenovicsova K, Vlkova B, Szemes T, Minarik G, Turňa J, Šebeková K (2010) Association of biochemical parameters and RAGE gene polymorphisms in healthy infants and their mothers. Clin Chim Acta 411(15–16):1034–1040PubMedCrossRef Boor P, Celec P, Klenovicsova K, Vlkova B, Szemes T, Minarik G, Turňa J, Šebeková K (2010) Association of biochemical parameters and RAGE gene polymorphisms in healthy infants and their mothers. Clin Chim Acta 411(15–16):1034–1040PubMedCrossRef
244.
Zurück zum Zitat Sasahira T, Kirita T, Bhawal UK, Yamamoto K, Ohmori H, Fujii K, Kuniyasu H (2007) Receptor for advanced glycation end products (RAGE) is important in the prediction of recurrence in human oral squamous cell carcinoma. Histopathology 51(2):166–172PubMedCrossRef Sasahira T, Kirita T, Bhawal UK, Yamamoto K, Ohmori H, Fujii K, Kuniyasu H (2007) Receptor for advanced glycation end products (RAGE) is important in the prediction of recurrence in human oral squamous cell carcinoma. Histopathology 51(2):166–172PubMedCrossRef
245.
Zurück zum Zitat Zhao C-B, Bao J-M, Lu Y-J, Zhao T, Zhou X-H, Zheng D-Y, Shan-Chao Z (2014) Co-expression of RAGE and HMGB1 is associated with cancer progression and poor patient outcome of prostate cancer. Am J Cancer Res 4(4):369PubMedPubMedCentral Zhao C-B, Bao J-M, Lu Y-J, Zhao T, Zhou X-H, Zheng D-Y, Shan-Chao Z (2014) Co-expression of RAGE and HMGB1 is associated with cancer progression and poor patient outcome of prostate cancer. Am J Cancer Res 4(4):369PubMedPubMedCentral
246.
Zurück zum Zitat Diederichs, Sven, Bulk, Etmar, Steffen, Björn, Ji, Ping, Tickenbrock, Lara, Lang Kerstin, Zänker Kurt S, Metzger, Ralf, Schneider Paul M, Gerke Volker. 2004. S100 family members and trypsinogens are predictors of distant metastasis and survival in early-stage non-small cell lung cancer. Cancer Res 64 (16):5564–5569 Diederichs, Sven, Bulk, Etmar, Steffen, Björn, Ji, Ping, Tickenbrock, Lara, Lang Kerstin, Zänker Kurt S, Metzger, Ralf, Schneider Paul M, Gerke Volker. 2004. S100 family members and trypsinogens are predictors of distant metastasis and survival in early-stage non-small cell lung cancer. Cancer Res 64 (16):5564–5569
247.
Metadaten
Titel
RAGE and Its Ligands: Molecular Interplay Between Glycation, Inflammation, and Hallmarks of Cancer—a Review
verfasst von
Gowri Palanissami
Solomon F. D. Paul
Publikationsdatum
09.07.2018
Verlag
Springer US
Erschienen in
Discover Oncology / Ausgabe 5/2018
Print ISSN: 1868-8497
Elektronische ISSN: 2730-6011
DOI
https://doi.org/10.1007/s12672-018-0342-9

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