Skip to main content
Erschienen in: Tumor Biology 2/2014

01.02.2014 | Review

Role of dysregulated expression of leptin and leptin receptors in colorectal carcinogenesis

verfasst von: Shahab Uddin, Azhar R. Hussain, Omar S. Khan, Khawla S. Al-Kuraya

Erschienen in: Tumor Biology | Ausgabe 2/2014

Einloggen, um Zugang zu erhalten

Abstract

Leptin is a multifunctional adipose-derived cytokine that plays a critical role in bodyweight homeostasis and energy balance. Plasma level of leptin is an indicator of the amount of energy stored in adipose tissues. Recently, leptin and leptin receptor dysregulation have been reported in a variety of malignant cells including colorectal cancers (CRCs). There are growing evidence that leptin may be the link between obesity and CRC carcinogenesis. Leptin influence the growth and proliferation of cancer cells via activation of various growth and survival signaling pathways including JAK/STAT, PI3-kinase/AKT, and/or MAP kinases. In this review, current understanding of leptin and its receptor’s roles in the pathogenesis of colonogenic cancer has been described.
Literatur
1.
Zurück zum Zitat Tartaglia LA, Dembski M, Weng X, Deng N, Culpepper J, Devos R, et al. Identification and expression cloning of a leptin receptor, Ob-R. Cell. 1995;83:1263–71.PubMedCrossRef Tartaglia LA, Dembski M, Weng X, Deng N, Culpepper J, Devos R, et al. Identification and expression cloning of a leptin receptor, Ob-R. Cell. 1995;83:1263–71.PubMedCrossRef
2.
Zurück zum Zitat Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature. 1994;372:425–32.PubMedCrossRef Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature. 1994;372:425–32.PubMedCrossRef
3.
Zurück zum Zitat Gorska E, Popko K, Stelmaszczyk-Emmel A, Ciepiela O, Kucharska A, Wasik M. Leptin receptors. Eur J Med Res. 2010;15 Suppl 2:50–4.PubMed Gorska E, Popko K, Stelmaszczyk-Emmel A, Ciepiela O, Kucharska A, Wasik M. Leptin receptors. Eur J Med Res. 2010;15 Suppl 2:50–4.PubMed
4.
Zurück zum Zitat Jung CH, Kim MS. Molecular mechanisms of central leptin resistance in obesity. Arch Pharm Res. 2013;36:201–7.PubMedCrossRef Jung CH, Kim MS. Molecular mechanisms of central leptin resistance in obesity. Arch Pharm Res. 2013;36:201–7.PubMedCrossRef
6.
Zurück zum Zitat Guffey CR, Fan D, Singh UP, Murphy EA. Linking obesity to colorectal cancer: recent insights into plausible biological mechanisms. Curr Opin Clin Nutr Metab Care. 2013;16:595–600.PubMedCrossRef Guffey CR, Fan D, Singh UP, Murphy EA. Linking obesity to colorectal cancer: recent insights into plausible biological mechanisms. Curr Opin Clin Nutr Metab Care. 2013;16:595–600.PubMedCrossRef
7.
Zurück zum Zitat Ogden CL, Carroll MD, Kit BK, Flegal KM. prevalence of obesity and trends in body mass index among us children and adolescents, 1999–2010. JAMA, J Am Med Assoc. 2012;307:483–90.CrossRef Ogden CL, Carroll MD, Kit BK, Flegal KM. prevalence of obesity and trends in body mass index among us children and adolescents, 1999–2010. JAMA, J Am Med Assoc. 2012;307:483–90.CrossRef
8.
Zurück zum Zitat Sun Z, Dragon S, Becker A, Gounni AS. Leptin inhibits neutrophil apoptosis in children via erk/nf-kappab-dependent pathways. PloS one. 2013;8:e55249.PubMedCentralPubMedCrossRef Sun Z, Dragon S, Becker A, Gounni AS. Leptin inhibits neutrophil apoptosis in children via erk/nf-kappab-dependent pathways. PloS one. 2013;8:e55249.PubMedCentralPubMedCrossRef
9.
Zurück zum Zitat Sheffield L. Malignant transformation of mammary epithelial cells increases expression of leptin and leptin receptor. Endocr Res. 2008;33:111–8.PubMedCrossRef Sheffield L. Malignant transformation of mammary epithelial cells increases expression of leptin and leptin receptor. Endocr Res. 2008;33:111–8.PubMedCrossRef
10.
Zurück zum Zitat Jemal A, Tiwari RC, Murray T, Ghafoor A, Samuels A, Ward E, et al. American Cancer S: cancer statistics, 2004. CA Cancer J Clin. 2004;54:8–29.PubMedCrossRef Jemal A, Tiwari RC, Murray T, Ghafoor A, Samuels A, Ward E, et al. American Cancer S: cancer statistics, 2004. CA Cancer J Clin. 2004;54:8–29.PubMedCrossRef
11.
Zurück zum Zitat Golan T, Urban D, Berger R, Lawrence YR. Changing prognosis of metastatic colorectal adenocarcinoma: differential improvement by age and tumor location. Cancer. 2013;119:3084–91.PubMedCrossRef Golan T, Urban D, Berger R, Lawrence YR. Changing prognosis of metastatic colorectal adenocarcinoma: differential improvement by age and tumor location. Cancer. 2013;119:3084–91.PubMedCrossRef
12.
Zurück zum Zitat Boeing H. Obesity and cancer–the update 2013. Best Pract Res Clin Endocrinol Metab. 2013;27:219–27.PubMedCrossRef Boeing H. Obesity and cancer–the update 2013. Best Pract Res Clin Endocrinol Metab. 2013;27:219–27.PubMedCrossRef
13.
14.
Zurück zum Zitat Terry PD, Miller AB, Rohan TE. Obesity and colorectal cancer risk in women. Gut. 2002;51:191–4.PubMedCrossRef Terry PD, Miller AB, Rohan TE. Obesity and colorectal cancer risk in women. Gut. 2002;51:191–4.PubMedCrossRef
15.
Zurück zum Zitat Stattin P, Lukanova A, Biessy C, Soderberg S, Palmqvist R, Kaaks R, et al. Obesity and colon cancer: does leptin provide a link? Int J Cancer. 2004;109:149–52.PubMedCrossRef Stattin P, Lukanova A, Biessy C, Soderberg S, Palmqvist R, Kaaks R, et al. Obesity and colon cancer: does leptin provide a link? Int J Cancer. 2004;109:149–52.PubMedCrossRef
16.
Zurück zum Zitat Sinicrope FA, Foster NR, Sargent DJ, O’Connell MJ, Rankin C. Obesity is an independent prognostic variable in colon cancer survivors. Clin Cancer Res. 2010;16:1884–93.PubMedCentralPubMedCrossRef Sinicrope FA, Foster NR, Sargent DJ, O’Connell MJ, Rankin C. Obesity is an independent prognostic variable in colon cancer survivors. Clin Cancer Res. 2010;16:1884–93.PubMedCentralPubMedCrossRef
17.
Zurück zum Zitat Bray GA. Medical consequences of obesity. J Clin Cancer Endocrinol Metab. 2004;89:2583–9.CrossRef Bray GA. Medical consequences of obesity. J Clin Cancer Endocrinol Metab. 2004;89:2583–9.CrossRef
18.
Zurück zum Zitat Liefers SC, te Pas MF, Veerkamp RF, van der Lende T. Associations between leptin gene polymorphisms and production, live weight, energy balance, feed intake, and fertility in holstein heifers. J Dairy Sci. 2002;85:1633–8.PubMedCrossRef Liefers SC, te Pas MF, Veerkamp RF, van der Lende T. Associations between leptin gene polymorphisms and production, live weight, energy balance, feed intake, and fertility in holstein heifers. J Dairy Sci. 2002;85:1633–8.PubMedCrossRef
20.
Zurück zum Zitat Gonullu G, Kahraman H, Bedir A, Bektas A, Yucel I. Association between adiponectin, resistin, insulin resistance, and colorectal tumors. Int J Colorectal Dis. 2010;25:205–12.PubMedCrossRef Gonullu G, Kahraman H, Bedir A, Bektas A, Yucel I. Association between adiponectin, resistin, insulin resistance, and colorectal tumors. Int J Colorectal Dis. 2010;25:205–12.PubMedCrossRef
21.
Zurück zum Zitat Erkasap N, Ozkurt M, Erkasap S, Yasar F, Uzuner K, Ihtiyar E, et al. Leptin receptor (Ob-R) mRNA expression and serum leptin concentration in patients with colorectal and metastatic colorectal cancer. Braz J Med Biol Res. 2013;46:306–10.PubMedCrossRef Erkasap N, Ozkurt M, Erkasap S, Yasar F, Uzuner K, Ihtiyar E, et al. Leptin receptor (Ob-R) mRNA expression and serum leptin concentration in patients with colorectal and metastatic colorectal cancer. Braz J Med Biol Res. 2013;46:306–10.PubMedCrossRef
22.
Zurück zum Zitat Tutino V, Notarnicola M, Guerra V, Lorusso D, Caruso MG. Increased soluble leptin receptor levels are associated with advanced tumor stage in colorectal cancer patients. Anticancer Res. 2011;31:3381–3.PubMed Tutino V, Notarnicola M, Guerra V, Lorusso D, Caruso MG. Increased soluble leptin receptor levels are associated with advanced tumor stage in colorectal cancer patients. Anticancer Res. 2011;31:3381–3.PubMed
23.
Zurück zum Zitat Song M, Zhang X, Wu K, Ogino S, Fuchs CS, Giovannucci EL, Chan AT. Plasma adiponectin and soluble leptin receptor and risk of colorectal cancer: a prospective study. Cancer Prev Res 2013 Song M, Zhang X, Wu K, Ogino S, Fuchs CS, Giovannucci EL, Chan AT. Plasma adiponectin and soluble leptin receptor and risk of colorectal cancer: a prospective study. Cancer Prev Res 2013
24.
Zurück zum Zitat Paik SS, Jang SM, Jang KS, Lee KH, Choi D, Jang SJ. Leptin expression correlates with favorable clinicopathologic phenotype and better prognosis in colorectal adenocarcinoma. Ann Surg Oncol. 2009;16:297–303.PubMedCrossRef Paik SS, Jang SM, Jang KS, Lee KH, Choi D, Jang SJ. Leptin expression correlates with favorable clinicopathologic phenotype and better prognosis in colorectal adenocarcinoma. Ann Surg Oncol. 2009;16:297–303.PubMedCrossRef
25.
Zurück zum Zitat Abolhassani M, Aloulou N, Chaumette MT, Aparicio T, Martin-Garcia N, Mansour H, et al. Leptin receptor-related immune response in colorectal tumors: the role of colonocytes and interleukin-8. Cancer Res. 2008;68:9423–32.PubMedCrossRef Abolhassani M, Aloulou N, Chaumette MT, Aparicio T, Martin-Garcia N, Mansour H, et al. Leptin receptor-related immune response in colorectal tumors: the role of colonocytes and interleukin-8. Cancer Res. 2008;68:9423–32.PubMedCrossRef
26.
Zurück zum Zitat Aloulou N, Bastuji-Garin S, Le Gouvello S, Abolhassani M, Chaumette MT, Charachon A, et al. Involvement of the leptin receptor in the immune response in intestinal cancer. Cancer Res. 2008;68:9413–22.PubMedCrossRef Aloulou N, Bastuji-Garin S, Le Gouvello S, Abolhassani M, Chaumette MT, Charachon A, et al. Involvement of the leptin receptor in the immune response in intestinal cancer. Cancer Res. 2008;68:9413–22.PubMedCrossRef
27.
Zurück zum Zitat Koda M, Sulkowska M, Kanczuga-Koda L, Surmacz E, Sulkowski S. Overexpression of the obesity hormone leptin in human colorectal cancer. J Clin Pathol. 2007;60:902–6.PubMedCrossRef Koda M, Sulkowska M, Kanczuga-Koda L, Surmacz E, Sulkowski S. Overexpression of the obesity hormone leptin in human colorectal cancer. J Clin Pathol. 2007;60:902–6.PubMedCrossRef
28.
Zurück zum Zitat Fenton JI, Lavigne JA, Perkins SN, Liu H, Chandramouli GV, Shih JH, et al. Microarray analysis reveals that leptin induces autocrine/paracrine cascades to promote survival and proliferation of colon epithelial cells in an apc genotype-dependent fashion. Mol Carcinog. 2008;47:9–21.PubMedCrossRef Fenton JI, Lavigne JA, Perkins SN, Liu H, Chandramouli GV, Shih JH, et al. Microarray analysis reveals that leptin induces autocrine/paracrine cascades to promote survival and proliferation of colon epithelial cells in an apc genotype-dependent fashion. Mol Carcinog. 2008;47:9–21.PubMedCrossRef
29.
Zurück zum Zitat Fenton JI, Hursting SD, Perkins SN, Hord NG. Interleukin-6 production induced by leptin treatment promotes cell proliferation in an apc (min/+) colon epithelial cell line. Carcinogenesis. 2006;27:1507–15.PubMedCrossRef Fenton JI, Hursting SD, Perkins SN, Hord NG. Interleukin-6 production induced by leptin treatment promotes cell proliferation in an apc (min/+) colon epithelial cell line. Carcinogenesis. 2006;27:1507–15.PubMedCrossRef
30.
Zurück zum Zitat FitzGerald AJ, Mandir N, Goodlad RA. Leptin, cell proliferation and crypt fission in the gastrointestinal tract of intravenously fed rats. Cell Prolif. 2005;38:25–33.PubMedCrossRef FitzGerald AJ, Mandir N, Goodlad RA. Leptin, cell proliferation and crypt fission in the gastrointestinal tract of intravenously fed rats. Cell Prolif. 2005;38:25–33.PubMedCrossRef
31.
Zurück zum Zitat Uddin S, Bavi PP, Hussain AR, Alsbeih G, Al-Sanea N, Abduljabbar A, et al. Leptin receptor expression in middle eastern colorectal cancer and its potential clinical implication. Carcinogenesis. 2009;30:1832–40.PubMedCrossRef Uddin S, Bavi PP, Hussain AR, Alsbeih G, Al-Sanea N, Abduljabbar A, et al. Leptin receptor expression in middle eastern colorectal cancer and its potential clinical implication. Carcinogenesis. 2009;30:1832–40.PubMedCrossRef
32.
Zurück zum Zitat Janeckova R. The role of leptin in human physiology and pathophysiology. Physiol Res Acad Sci Bohemoslov. 2001;50:443–59. Janeckova R. The role of leptin in human physiology and pathophysiology. Physiol Res Acad Sci Bohemoslov. 2001;50:443–59.
33.
Zurück zum Zitat Considine RV, Sinha MK, Heiman ML, Kriauciunas A, Stephens TW, Nyce MR, et al. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. New Engl J Med. 1996;334:292–5.PubMedCrossRef Considine RV, Sinha MK, Heiman ML, Kriauciunas A, Stephens TW, Nyce MR, et al. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. New Engl J Med. 1996;334:292–5.PubMedCrossRef
34.
Zurück zum Zitat Liu L, Zhong R, Wei S, Xiang H, Chen J, Xie D, et al. The leptin gene family and colorectal cancer: interaction with smoking behavior and family history of cancer. PLoS ONE. 2013;8:e60777.PubMedCentralPubMedCrossRef Liu L, Zhong R, Wei S, Xiang H, Chen J, Xie D, et al. The leptin gene family and colorectal cancer: interaction with smoking behavior and family history of cancer. PLoS ONE. 2013;8:e60777.PubMedCentralPubMedCrossRef
35.
Zurück zum Zitat Ahima RS, Prabakaran D, Mantzoros C, Qu D, Lowell B, Maratos-Flier E, et al. Role of leptin in the neuroendocrine response to fasting. Nature. 1996;382:250–2.PubMedCrossRef Ahima RS, Prabakaran D, Mantzoros C, Qu D, Lowell B, Maratos-Flier E, et al. Role of leptin in the neuroendocrine response to fasting. Nature. 1996;382:250–2.PubMedCrossRef
36.
Zurück zum Zitat Chua Jr SC, Chung WK, Wu-Peng XS, Zhang Y, Liu SM, Tartaglia L, et al. Phenotypes of mouse diabetes and rat fatty due to mutations in the ob (leptin) receptor. Science. 1996;271:994–6.PubMedCrossRef Chua Jr SC, Chung WK, Wu-Peng XS, Zhang Y, Liu SM, Tartaglia L, et al. Phenotypes of mouse diabetes and rat fatty due to mutations in the ob (leptin) receptor. Science. 1996;271:994–6.PubMedCrossRef
37.
38.
Zurück zum Zitat Lin J, Barb CR, Matteri RL, Kraeling RR, Chen X, Meinersmann RJ, et al. Long form leptin receptor mRNA expression in the brain, pituitary, and other tissues in the pig. Dom Animal Endocrinol. 2000;19:53–61.CrossRef Lin J, Barb CR, Matteri RL, Kraeling RR, Chen X, Meinersmann RJ, et al. Long form leptin receptor mRNA expression in the brain, pituitary, and other tissues in the pig. Dom Animal Endocrinol. 2000;19:53–61.CrossRef
39.
Zurück zum Zitat Caprio M, Fabbrini E, Isidori AM, Aversa A, Fabbri A. Leptin in reproduction. Trends Endocrinol Metabol TEM. 2001;12:65–72.CrossRef Caprio M, Fabbrini E, Isidori AM, Aversa A, Fabbri A. Leptin in reproduction. Trends Endocrinol Metabol TEM. 2001;12:65–72.CrossRef
40.
Zurück zum Zitat Bartucci M, Svensson S, Ricci-Vitiani L, Dattilo R, Biffoni M, Signore M, et al. Obesity hormone leptin induces growth and interferes with the cytotoxic effects of 5-fluorouracil in colorectal tumor stem cells. Endocrine Rel Cancer. 2010;17:823–33.CrossRef Bartucci M, Svensson S, Ricci-Vitiani L, Dattilo R, Biffoni M, Signore M, et al. Obesity hormone leptin induces growth and interferes with the cytotoxic effects of 5-fluorouracil in colorectal tumor stem cells. Endocrine Rel Cancer. 2010;17:823–33.CrossRef
41.
Zurück zum Zitat Birmingham JM, Busik JV, Hansen-Smith FM, Fenton JI. Novel mechanism for obesity-induced colon cancer progression. Carcinogenesis. 2009;30:690–7.PubMedCrossRef Birmingham JM, Busik JV, Hansen-Smith FM, Fenton JI. Novel mechanism for obesity-induced colon cancer progression. Carcinogenesis. 2009;30:690–7.PubMedCrossRef
42.
Zurück zum Zitat Amemori S, Ootani A, Aoki S, Fujise T, Shimoda R, Kakimoto T, et al. Adipocytes and preadipocytes promote the proliferation of colon cancer cells in vitro. Am J Physiol Gastrointest Liver Physiol. 2007;292:G923–9.PubMedCrossRef Amemori S, Ootani A, Aoki S, Fujise T, Shimoda R, Kakimoto T, et al. Adipocytes and preadipocytes promote the proliferation of colon cancer cells in vitro. Am J Physiol Gastrointest Liver Physiol. 2007;292:G923–9.PubMedCrossRef
43.
Zurück zum Zitat Saxena NK, Sharma D, Ding X, Lin S, Marra F, Merlin D, et al. Concomitant activation of the JAK/STAT, PI3K/AKT, and ERK signaling is involved in leptin-mediated promotion of invasion and migration of hepatocellular carcinoma cells. Cancer Res. 2007;67:2497–507.PubMedCentralPubMedCrossRef Saxena NK, Sharma D, Ding X, Lin S, Marra F, Merlin D, et al. Concomitant activation of the JAK/STAT, PI3K/AKT, and ERK signaling is involved in leptin-mediated promotion of invasion and migration of hepatocellular carcinoma cells. Cancer Res. 2007;67:2497–507.PubMedCentralPubMedCrossRef
44.
Zurück zum Zitat Huang XF, Chen JZ. Obesity, the PI3K/AKT signal pathway and colon cancer. Obes Rev. 2009;10:610–16.PubMedCrossRef Huang XF, Chen JZ. Obesity, the PI3K/AKT signal pathway and colon cancer. Obes Rev. 2009;10:610–16.PubMedCrossRef
45.
Zurück zum Zitat Ogunwobi OO, Beales IL. Cyclo-oxygenase-independent inhibition of apoptosis and stimulation of proliferation by leptin in human colon cancer cells. Dig Dis Sci. 2007;52:1934–45.PubMedCrossRef Ogunwobi OO, Beales IL. Cyclo-oxygenase-independent inhibition of apoptosis and stimulation of proliferation by leptin in human colon cancer cells. Dig Dis Sci. 2007;52:1934–45.PubMedCrossRef
46.
Zurück zum Zitat Bjorbaek C, Uotani S, da Silva B, Flier JS. Divergent signaling capacities of the long and short isoforms of the leptin receptor. J Biol Chem. 1997;272:32686–95.PubMedCrossRef Bjorbaek C, Uotani S, da Silva B, Flier JS. Divergent signaling capacities of the long and short isoforms of the leptin receptor. J Biol Chem. 1997;272:32686–95.PubMedCrossRef
47.
Zurück zum Zitat Sharma D, Saxena NK, Vertino PM, Anania FA. Leptin promotes the proliferative response and invasiveness in human endometrial cancer cells by activating multiple signal-transduction pathways. Endocrine Rel Cancer. 2006;13:629–40.CrossRef Sharma D, Saxena NK, Vertino PM, Anania FA. Leptin promotes the proliferative response and invasiveness in human endometrial cancer cells by activating multiple signal-transduction pathways. Endocrine Rel Cancer. 2006;13:629–40.CrossRef
48.
Zurück zum Zitat Deo DD, Rao AP, Bose SS, Ouhtit A, Baliga SB, Rao SA, et al. Differential effects of leptin on the invasive potential of androgen-dependent and -independent prostate carcinoma cells. J Biomed Biotechnol. 2008;2008:163902.PubMedCentralPubMedCrossRef Deo DD, Rao AP, Bose SS, Ouhtit A, Baliga SB, Rao SA, et al. Differential effects of leptin on the invasive potential of androgen-dependent and -independent prostate carcinoma cells. J Biomed Biotechnol. 2008;2008:163902.PubMedCentralPubMedCrossRef
49.
Zurück zum Zitat Gao J, Tian J, Lv Y, Shi F, Kong F, Shi H, et al. Leptin induces functional activation of cyclooxygenase-2 through JAK2/STAT3, MAPK/ERK, and PI3K/AKT pathways in human endometrial cancer cells. Cancer Sci. 2009;100:389–95.PubMedCrossRef Gao J, Tian J, Lv Y, Shi F, Kong F, Shi H, et al. Leptin induces functional activation of cyclooxygenase-2 through JAK2/STAT3, MAPK/ERK, and PI3K/AKT pathways in human endometrial cancer cells. Cancer Sci. 2009;100:389–95.PubMedCrossRef
50.
Zurück zum Zitat Beales IL, Ogunwobi OO. Leptin synergistically enhances the anti-apoptotic and growth-promoting effects of acid in oe33 oesophageal adenocarcinoma cells in culture. Mol Cell Endocrinol. 2007;274:60–8.PubMedCrossRef Beales IL, Ogunwobi OO. Leptin synergistically enhances the anti-apoptotic and growth-promoting effects of acid in oe33 oesophageal adenocarcinoma cells in culture. Mol Cell Endocrinol. 2007;274:60–8.PubMedCrossRef
51.
Zurück zum Zitat Quintas-Cardama A, Verstovsek S. Molecular pathways: JAK/STAT pathway: mutations, inhibitors, and resistance. Clin Cancer Res. 2013;19:1933–40.PubMedCrossRef Quintas-Cardama A, Verstovsek S. Molecular pathways: JAK/STAT pathway: mutations, inhibitors, and resistance. Clin Cancer Res. 2013;19:1933–40.PubMedCrossRef
52.
Zurück zum Zitat Yu JH, Kim H. Role of Janus kinase/signal transducers and activators of transcription in the pathogenesis of pancreatitis and pancreatic cancer. Gut Liver. 2012;6:417–22.PubMedCentralPubMedCrossRef Yu JH, Kim H. Role of Janus kinase/signal transducers and activators of transcription in the pathogenesis of pancreatitis and pancreatic cancer. Gut Liver. 2012;6:417–22.PubMedCentralPubMedCrossRef
53.
Zurück zum Zitat Singh N, Hussain S, Bharadwaj M, Kakkar N, Singh SK, Sobti RC. Overexpression of signal transducer and activator of transcription (stat-3 and stat-5) transcription factors and alteration of suppressor of cytokine signaling (socs-1) protein in prostate cancer. J Recept Signal Transduct Res. 2012;32:321–27.PubMedCrossRef Singh N, Hussain S, Bharadwaj M, Kakkar N, Singh SK, Sobti RC. Overexpression of signal transducer and activator of transcription (stat-3 and stat-5) transcription factors and alteration of suppressor of cytokine signaling (socs-1) protein in prostate cancer. J Recept Signal Transduct Res. 2012;32:321–27.PubMedCrossRef
54.
Zurück zum Zitat Ma XT, Wang S, Ye YJ, Du RY, Cui ZR, Somsouk M. Constitutive activation of STAT3 signaling pathway in human colorectal carcinoma. World J Gastroentorol WJG. 2004;10:1569–73. Ma XT, Wang S, Ye YJ, Du RY, Cui ZR, Somsouk M. Constitutive activation of STAT3 signaling pathway in human colorectal carcinoma. World J Gastroentorol WJG. 2004;10:1569–73.
55.
Zurück zum Zitat Osaki LH, Gama P. Mapks and signal transduction in the control of gastrointestinal epithelial cell proliferation and differentiation. Int J Mol Sci. 2013;14:10143–61.PubMedCentralPubMedCrossRef Osaki LH, Gama P. Mapks and signal transduction in the control of gastrointestinal epithelial cell proliferation and differentiation. Int J Mol Sci. 2013;14:10143–61.PubMedCentralPubMedCrossRef
56.
Zurück zum Zitat Taylor CA, Zheng Q, Liu Z, Thompson JE. Role of p38 and jnk mapk signaling pathways and tumor suppressor p53 on induction of apoptosis in response to ad-eif5a1 in a549 lung cancer cells. Mol Cancer. 2013;12:35.PubMedCentralPubMedCrossRef Taylor CA, Zheng Q, Liu Z, Thompson JE. Role of p38 and jnk mapk signaling pathways and tumor suppressor p53 on induction of apoptosis in response to ad-eif5a1 in a549 lung cancer cells. Mol Cancer. 2013;12:35.PubMedCentralPubMedCrossRef
57.
Zurück zum Zitat Weston CR, Lambright DG, Davis RJ. Signal transduction. MAP kinase signaling specificity. Science. 2002;296:2345–7.PubMedCrossRef Weston CR, Lambright DG, Davis RJ. Signal transduction. MAP kinase signaling specificity. Science. 2002;296:2345–7.PubMedCrossRef
58.
Zurück zum Zitat Hegyi K, Fulop K, Kovacs K, Toth S, Falus A. Leptin-induced signal transduction pathways. Cell Biol Int. 2004;28:159–69.PubMedCrossRef Hegyi K, Fulop K, Kovacs K, Toth S, Falus A. Leptin-induced signal transduction pathways. Cell Biol Int. 2004;28:159–69.PubMedCrossRef
59.
Zurück zum Zitat van den Brink GR, O’Toole T, Hardwick JC, van den Boogaardt DE, Versteeg HH, van Deventer SJ, et al. Leptin signaling in human peripheral blood mononuclear cells, activation of p38 and p42/44 mitogen-activated protein (map) kinase and p70 s6 kinase. Mol Cell Biol Res Comm MCBRC. 2000;4:144–50.CrossRef van den Brink GR, O’Toole T, Hardwick JC, van den Boogaardt DE, Versteeg HH, van Deventer SJ, et al. Leptin signaling in human peripheral blood mononuclear cells, activation of p38 and p42/44 mitogen-activated protein (map) kinase and p70 s6 kinase. Mol Cell Biol Res Comm MCBRC. 2000;4:144–50.CrossRef
60.
Zurück zum Zitat Dreyer MG, Juge-Aubry CE, Gabay C, Lang U, Rohner-Jeanrenaud F, Dayer JM, et al. Leptin activates the promoter of the interleukin-1 receptor antagonist through p42/44 mitogen-activated protein kinase and a composite nuclear factor kappa b/pu.1 binding site. Biochem J. 2003;370:591–9.PubMedCrossRef Dreyer MG, Juge-Aubry CE, Gabay C, Lang U, Rohner-Jeanrenaud F, Dayer JM, et al. Leptin activates the promoter of the interleukin-1 receptor antagonist through p42/44 mitogen-activated protein kinase and a composite nuclear factor kappa b/pu.1 binding site. Biochem J. 2003;370:591–9.PubMedCrossRef
61.
Zurück zum Zitat Ogunwobi O, Mutungi G, Beales IL. Leptin stimulates proliferation and inhibits apoptosis in barrett’s esophageal adenocarcinoma cells by cyclooxygenase-2-dependent, prostaglandin-e2-mediated transactivation of the epidermal growth factor receptor and c-jun nh2-terminal kinase activation. Endocrinology. 2006;147:4505–16.PubMedCrossRef Ogunwobi O, Mutungi G, Beales IL. Leptin stimulates proliferation and inhibits apoptosis in barrett’s esophageal adenocarcinoma cells by cyclooxygenase-2-dependent, prostaglandin-e2-mediated transactivation of the epidermal growth factor receptor and c-jun nh2-terminal kinase activation. Endocrinology. 2006;147:4505–16.PubMedCrossRef
62.
Zurück zum Zitat Sun Y, Sinicrope FA. Selective inhibitors of mek1/erk44/42 and p38 mitogen-activated protein kinases potentiate apoptosis induction by sulindac sulfide in human colon carcinoma cells. Mol Cancer Ther. 2005;4:51–9.PubMed Sun Y, Sinicrope FA. Selective inhibitors of mek1/erk44/42 and p38 mitogen-activated protein kinases potentiate apoptosis induction by sulindac sulfide in human colon carcinoma cells. Mol Cancer Ther. 2005;4:51–9.PubMed
63.
Zurück zum Zitat Nishihara H, Hwang M, Kizaka-Kondoh S, Eckmann L, Insel PA. Cyclic amp promotes camp-responsive element-binding protein-dependent induction of cellular inhibitor of apoptosis protein-2 and suppresses apoptosis of colon cancer cells through erk1/2 and p38 mapk. J Biol Chem. 2004;279:26176–83.PubMedCrossRef Nishihara H, Hwang M, Kizaka-Kondoh S, Eckmann L, Insel PA. Cyclic amp promotes camp-responsive element-binding protein-dependent induction of cellular inhibitor of apoptosis protein-2 and suppresses apoptosis of colon cancer cells through erk1/2 and p38 mapk. J Biol Chem. 2004;279:26176–83.PubMedCrossRef
64.
Zurück zum Zitat Chan UP, Lee JF, Wang SH, Leung KL, Chen GG. Induction of colon cancer cell death by 7-hydroxystaurosporine (ucn-01) is associated with increased p38 mapk and decreased bcl-xl. Anti Canc Drugs. 2003;14:761–6.CrossRef Chan UP, Lee JF, Wang SH, Leung KL, Chen GG. Induction of colon cancer cell death by 7-hydroxystaurosporine (ucn-01) is associated with increased p38 mapk and decreased bcl-xl. Anti Canc Drugs. 2003;14:761–6.CrossRef
65.
Zurück zum Zitat Lee EJ, Park HG, Kang HS. Sodium salicylate induces apoptosis in hct116 colorectal cancer cells through activation of p38mapk. Int J Oncol. 2003;23:503–8.PubMed Lee EJ, Park HG, Kang HS. Sodium salicylate induces apoptosis in hct116 colorectal cancer cells through activation of p38mapk. Int J Oncol. 2003;23:503–8.PubMed
66.
Zurück zum Zitat Hussain AR, Ahmed SO, Ahmed M, Khan OS, Al Abdulmohsen S, Platanias LC, et al. Cross-talk between nfkb and the PI3-kinase/AKT pathway can be targeted in primary effusion lymphoma (pel) cell lines for efficient apoptosis. PLoS ONE. 2012;7:e39945.PubMedCentralPubMedCrossRef Hussain AR, Ahmed SO, Ahmed M, Khan OS, Al Abdulmohsen S, Platanias LC, et al. Cross-talk between nfkb and the PI3-kinase/AKT pathway can be targeted in primary effusion lymphoma (pel) cell lines for efficient apoptosis. PLoS ONE. 2012;7:e39945.PubMedCentralPubMedCrossRef
67.
Zurück zum Zitat Li W, Wang H, Kuang CY, Zhu JK, Yu Y, Qin ZX, et al. An essential role for the id1/pi3k/akt/nfkb/survivin signalling pathway in promoting the proliferation of endothelial progenitor cells in vitro. Mol Cell Biochem. 2012;363:135–45.PubMedCentralPubMedCrossRef Li W, Wang H, Kuang CY, Zhu JK, Yu Y, Qin ZX, et al. An essential role for the id1/pi3k/akt/nfkb/survivin signalling pathway in promoting the proliferation of endothelial progenitor cells in vitro. Mol Cell Biochem. 2012;363:135–45.PubMedCentralPubMedCrossRef
68.
Zurück zum Zitat Rayet B, Gelinas C. Aberrant rel/nfkb genes and activity in human cancer. Oncogene. 1999;18:6938–47.PubMedCrossRef Rayet B, Gelinas C. Aberrant rel/nfkb genes and activity in human cancer. Oncogene. 1999;18:6938–47.PubMedCrossRef
69.
Zurück zum Zitat Carpenter CL, Duckworth BC, Auger KR, Cohen B, Schaffhausen BS, Cantley LC. Purification and characterization of phosphoinositide 3-kinase from rat liver. J Biol Chem. 1990;265:19704–11.PubMed Carpenter CL, Duckworth BC, Auger KR, Cohen B, Schaffhausen BS, Cantley LC. Purification and characterization of phosphoinositide 3-kinase from rat liver. J Biol Chem. 1990;265:19704–11.PubMed
70.
Zurück zum Zitat Chen HC, Guan JL. Association of focal adhesion kinase with its potential substrate phosphatidylinositol 3-kinase. Proc Natl Acad Sci U S A. 1994;91:10148–52.PubMedCentralPubMedCrossRef Chen HC, Guan JL. Association of focal adhesion kinase with its potential substrate phosphatidylinositol 3-kinase. Proc Natl Acad Sci U S A. 1994;91:10148–52.PubMedCentralPubMedCrossRef
72.
Zurück zum Zitat Jiang BH, Aoki M, Zheng JZ, Li J, Vogt PK. Myogenic signaling of phosphatidylinositol 3-kinase requires the serine-threonine kinase akt/protein kinase b. Proc Natl Acad Sci U S A. 1999;96:2077–81.PubMedCentralPubMedCrossRef Jiang BH, Aoki M, Zheng JZ, Li J, Vogt PK. Myogenic signaling of phosphatidylinositol 3-kinase requires the serine-threonine kinase akt/protein kinase b. Proc Natl Acad Sci U S A. 1999;96:2077–81.PubMedCentralPubMedCrossRef
73.
Zurück zum Zitat Uddin S, Bu R, Ahmed M, Abubaker J, Al-Dayel F, Bavi P, et al. Overexpression of leptin receptor predicts an unfavorable outcome in middle eastern ovarian cancer. Mol Cancer. 2009;8:74.PubMedCentralPubMedCrossRef Uddin S, Bu R, Ahmed M, Abubaker J, Al-Dayel F, Bavi P, et al. Overexpression of leptin receptor predicts an unfavorable outcome in middle eastern ovarian cancer. Mol Cancer. 2009;8:74.PubMedCentralPubMedCrossRef
74.
Zurück zum Zitat Uddin S, Bavi P, Siraj AK, Ahmed M, Al-Rasheed M, Hussain AR, et al. Leptin-r and its association with PI3K/AKT signaling pathway in papillary thyroid carcinoma. Endocrine Rel Cancer. 2010;17:191–202.CrossRef Uddin S, Bavi P, Siraj AK, Ahmed M, Al-Rasheed M, Hussain AR, et al. Leptin-r and its association with PI3K/AKT signaling pathway in papillary thyroid carcinoma. Endocrine Rel Cancer. 2010;17:191–202.CrossRef
75.
Zurück zum Zitat Wang D, Chen J, Chen H, Duan Z, Xu Q, Wei M, et al. Leptin regulates proliferation and apoptosis of colorectal carcinoma through PI3K/AKT/mTOR signalling pathway. J Biosci. 2012;37:91–101.PubMedCrossRef Wang D, Chen J, Chen H, Duan Z, Xu Q, Wei M, et al. Leptin regulates proliferation and apoptosis of colorectal carcinoma through PI3K/AKT/mTOR signalling pathway. J Biosci. 2012;37:91–101.PubMedCrossRef
76.
Zurück zum Zitat Rao CV, Janakiram NB, Mohammed A. Lipoxygenase and cyclooxygenase pathways and colorectal cancer prevention. Curr Colorectal Cancer Rep. 2012;8:316–24.PubMedCentralPubMedCrossRef Rao CV, Janakiram NB, Mohammed A. Lipoxygenase and cyclooxygenase pathways and colorectal cancer prevention. Curr Colorectal Cancer Rep. 2012;8:316–24.PubMedCentralPubMedCrossRef
77.
Zurück zum Zitat Muller-Decker K. Cyclooxygenase-dependent signaling is causally linked to non-melanoma skin carcinogenesis: pharmacological, genetic, and clinical evidence. Canc Metastasis Rev. 2011;30:343–61.CrossRef Muller-Decker K. Cyclooxygenase-dependent signaling is causally linked to non-melanoma skin carcinogenesis: pharmacological, genetic, and clinical evidence. Canc Metastasis Rev. 2011;30:343–61.CrossRef
78.
Zurück zum Zitat Liu CH, Chang SH, Narko K, Trifan OC, Wu MT, Smith E, et al. Overexpression of cyclooxygenase-2 is sufficient to induce tumorigenesis in transgenic mice. J Biol Chem. 2001;276:18563–69.PubMedCrossRef Liu CH, Chang SH, Narko K, Trifan OC, Wu MT, Smith E, et al. Overexpression of cyclooxygenase-2 is sufficient to induce tumorigenesis in transgenic mice. J Biol Chem. 2001;276:18563–69.PubMedCrossRef
79.
Zurück zum Zitat Tsujii M, Kawano S, Tsuji S, Sawaoka H, Hori M, DuBois RN. Cyclooxygenase regulates angiogenesis induced by colon cancer cells. Cell. 1998;93:705–16.PubMedCrossRef Tsujii M, Kawano S, Tsuji S, Sawaoka H, Hori M, DuBois RN. Cyclooxygenase regulates angiogenesis induced by colon cancer cells. Cell. 1998;93:705–16.PubMedCrossRef
80.
Zurück zum Zitat Perlikos F, Harrington KJ, Syrigos KN. Key molecular mechanisms in lung cancer invasion and metastasis: a comprehensive review. Crit Rev Oncol Hematol. 2013;87:1–11.PubMedCrossRef Perlikos F, Harrington KJ, Syrigos KN. Key molecular mechanisms in lung cancer invasion and metastasis: a comprehensive review. Crit Rev Oncol Hematol. 2013;87:1–11.PubMedCrossRef
81.
Zurück zum Zitat Bhave SL, Teknos TN, Pan Q. Molecular parameters of head and neck cancer metastasis. Crit Rev Eukaryot Gen Expr. 21:143–53. Bhave SL, Teknos TN, Pan Q. Molecular parameters of head and neck cancer metastasis. Crit Rev Eukaryot Gen Expr. 21:143–53.
82.
Zurück zum Zitat Salzmann S, Seher A, Trebing J, Weisenberger D, Rosenthal A, Siegmund D, et al. Fibroblast growth factor inducible (fn14)-specific antibodies concomitantly display signaling pathway-specific agonistic and antagonistic activity. J Biol Chem. 2013;288:13455–66.PubMedCrossRef Salzmann S, Seher A, Trebing J, Weisenberger D, Rosenthal A, Siegmund D, et al. Fibroblast growth factor inducible (fn14)-specific antibodies concomitantly display signaling pathway-specific agonistic and antagonistic activity. J Biol Chem. 2013;288:13455–66.PubMedCrossRef
83.
Zurück zum Zitat Sarfstein R, Werner H. Minireview: nuclear insulin and insulin-like growth factor-1 receptors: a novel paradigm in signal transduction. Endocrinology. 2013;154:1672–79.PubMedCrossRef Sarfstein R, Werner H. Minireview: nuclear insulin and insulin-like growth factor-1 receptors: a novel paradigm in signal transduction. Endocrinology. 2013;154:1672–79.PubMedCrossRef
84.
Zurück zum Zitat Chan CM, Chang HH, Wang VC, Huang CL, Hung CF. Inhibitory effects of resveratrol on pdgf-bb-induced retinal pigment epithelial cell migration via pdgfrbeta, pi3k/akt and mapk pathways. PloS ONE. 2013;8:e56819.PubMedCentralPubMedCrossRef Chan CM, Chang HH, Wang VC, Huang CL, Hung CF. Inhibitory effects of resveratrol on pdgf-bb-induced retinal pigment epithelial cell migration via pdgfrbeta, pi3k/akt and mapk pathways. PloS ONE. 2013;8:e56819.PubMedCentralPubMedCrossRef
85.
Zurück zum Zitat Stattin P, Palmqvist R, Soderberg S, Biessy C, Ardnor B, Hallmans G, et al. Plasma leptin and colorectal cancer risk: a prospective study in northern sweden. Oncol Rep. 2003;10:2015–21.PubMed Stattin P, Palmqvist R, Soderberg S, Biessy C, Ardnor B, Hallmans G, et al. Plasma leptin and colorectal cancer risk: a prospective study in northern sweden. Oncol Rep. 2003;10:2015–21.PubMed
86.
Zurück zum Zitat Sierra-Honigmann MR, Nath AK, Murakami C, Garcia-Cardena G, Papapetropoulos A, Sessa WC, et al. Biological action of leptin as an angiogenic factor. Science. 1998;281:1683–6.PubMedCrossRef Sierra-Honigmann MR, Nath AK, Murakami C, Garcia-Cardena G, Papapetropoulos A, Sessa WC, et al. Biological action of leptin as an angiogenic factor. Science. 1998;281:1683–6.PubMedCrossRef
87.
Zurück zum Zitat Hardwick JC, Van Den Brink GR, Offerhaus GJ, Van Deventer SJ, Peppelenbosch MP. Leptin is a growth factor for colonic epithelial cells. Gastroenterology. 2001;121:79–90.PubMedCrossRef Hardwick JC, Van Den Brink GR, Offerhaus GJ, Van Deventer SJ, Peppelenbosch MP. Leptin is a growth factor for colonic epithelial cells. Gastroenterology. 2001;121:79–90.PubMedCrossRef
88.
Zurück zum Zitat Attoub S, Noe V, Pirola L, Bruyneel E, Chastre E, Mareel M, et al. Leptin promotes invasiveness of kidney and colonic epithelial cells via phosphoinositide 3-kinase-, rho-, and rac-dependent signaling pathways. FASEB J. 2000;14:2329–38.PubMedCrossRef Attoub S, Noe V, Pirola L, Bruyneel E, Chastre E, Mareel M, et al. Leptin promotes invasiveness of kidney and colonic epithelial cells via phosphoinositide 3-kinase-, rho-, and rac-dependent signaling pathways. FASEB J. 2000;14:2329–38.PubMedCrossRef
89.
Zurück zum Zitat Liu Z, Uesaka T, Watanabe H, Kato N. High fat diet enhances colonic cell proliferation and carcinogenesis in rats by elevating serum leptin. Int J Oncol. 2001;19:1009–14.PubMed Liu Z, Uesaka T, Watanabe H, Kato N. High fat diet enhances colonic cell proliferation and carcinogenesis in rats by elevating serum leptin. Int J Oncol. 2001;19:1009–14.PubMed
90.
Zurück zum Zitat Fox SB, Gasparini G, Harris AL. Angiogenesis: pathological, prognostic, and growth-factor pathways and their link to trial design and anticancer drugs. Lancet Oncol. 2001;2:278–89.PubMedCrossRef Fox SB, Gasparini G, Harris AL. Angiogenesis: pathological, prognostic, and growth-factor pathways and their link to trial design and anticancer drugs. Lancet Oncol. 2001;2:278–89.PubMedCrossRef
Metadaten
Titel
Role of dysregulated expression of leptin and leptin receptors in colorectal carcinogenesis
verfasst von
Shahab Uddin
Azhar R. Hussain
Omar S. Khan
Khawla S. Al-Kuraya
Publikationsdatum
01.02.2014
Verlag
Springer Netherlands
Erschienen in
Tumor Biology / Ausgabe 2/2014
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-013-1166-4

Weitere Artikel der Ausgabe 2/2014

Tumor Biology 2/2014 Zur Ausgabe

Adjuvante Immuntherapie verlängert Leben bei RCC

25.04.2024 Nierenkarzinom Nachrichten

Nun gibt es auch Resultate zum Gesamtüberleben: Eine adjuvante Pembrolizumab-Therapie konnte in einer Phase-3-Studie das Leben von Menschen mit Nierenzellkarzinom deutlich verlängern. Die Sterberate war im Vergleich zu Placebo um 38% geringer.

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

25.04.2024 NSCLC Nachrichten

Das Risiko für Rezidiv oder Tod von Patienten und Patientinnen mit reseziertem ALK-positivem NSCLC ist unter einer adjuvanten Therapie mit dem Tyrosinkinase-Inhibitor Alectinib signifikant geringer als unter platinbasierter Chemotherapie.

Bei Senioren mit Prostatakarzinom auf Anämie achten!

24.04.2024 DGIM 2024 Nachrichten

Patienten, die zur Behandlung ihres Prostatakarzinoms eine Androgendeprivationstherapie erhalten, entwickeln nicht selten eine Anämie. Wer ältere Patienten internistisch mitbetreut, sollte auf diese Nebenwirkung achten.

ICI-Therapie in der Schwangerschaft wird gut toleriert

Müssen sich Schwangere einer Krebstherapie unterziehen, rufen Immuncheckpointinhibitoren offenbar nicht mehr unerwünschte Wirkungen hervor als andere Mittel gegen Krebs.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.