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Erschienen in: Tumor Biology 6/2015

01.06.2015 | Review

Emerging role of silent information regulator 1 (SIRT1) in hepatocellular carcinoma: a potential therapeutic target

verfasst von: Yuting Wu, Xiaoming Meng, Cheng Huang, Jun Li

Erschienen in: Tumor Biology | Ausgabe 6/2015

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Abstract

Hepatocellular carcinoma (HCC) is one of the most prevalent neoplasms worldwide, ranking as the second leading cause of cancer-related death due to its high invasive and metastatic potential. SIRT1 (silent information regulator 1), a member of mammalian sirtuin family protein (SIRT1–SIRT7), functions as a conserved nicotinamide adenine dinucleotide (NAD)+-dependent deacetylase to implicate in the modulation of transcriptional silencing and cell survival. Recently, except for the regulatory role of SIRT1 in various biological processes, the carcinogenesis effect of SIRT1 was revealed in HCC. Importantly, SIRT1 was confirmed to be involved in tumorigenesis, metastasis, prognosis, and chemical resistant of HCC, as a result of its deacetylation of oncogenic or tumor suppressor factors. The focus of this review was to delineate the carcinogenesis effects of SIRT1 on HCC and present an overview of SIRT1 functions in normal liver followed by SIRT1 roles in HCC, with focus on the underlying molecular mechanism to promote SIRT1 as a new therapeutic target for HCC.
Literatur
1.
Zurück zum Zitat El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology. 2007;132:2557–76.PubMed El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology. 2007;132:2557–76.PubMed
2.
Zurück zum Zitat Carter D. New global survey shows an increasing cancer burden. Am J Nurs. 2014;114:17. Carter D. New global survey shows an increasing cancer burden. Am J Nurs. 2014;114:17.
3.
Zurück zum Zitat El-Serag HB, Tran T, Everhart JE. Diabetes increases the risk of chronic liver disease and hepatocellular carcinoma. Gastroenterology. 2004;126:460–8.PubMed El-Serag HB, Tran T, Everhart JE. Diabetes increases the risk of chronic liver disease and hepatocellular carcinoma. Gastroenterology. 2004;126:460–8.PubMed
4.
Zurück zum Zitat Ruhl CE, Everhart JE. Determinants of the association of overweight with elevated serum alanine aminotransferase activity in the United States. Gastroenterology. 2003;124:71–9.PubMed Ruhl CE, Everhart JE. Determinants of the association of overweight with elevated serum alanine aminotransferase activity in the United States. Gastroenterology. 2003;124:71–9.PubMed
5.
Zurück zum Zitat Chuang SC, La Vecchia C, Boffetta P. Liver cancer: descriptive epidemiology and risk factors other than HBV and HCV infection. Cancer Lett. 2009;286:9–14.PubMed Chuang SC, La Vecchia C, Boffetta P. Liver cancer: descriptive epidemiology and risk factors other than HBV and HCV infection. Cancer Lett. 2009;286:9–14.PubMed
6.
Zurück zum Zitat Chen W, Zheng R, Zhang S, Zhao P, Zeng H, Zou X, et al. Annual report on status of cancer in China, 2010. Chin J Cancer Res = Chung-kuo yen cheng yen chiu. 2014;26:48–58.PubMed Chen W, Zheng R, Zhang S, Zhao P, Zeng H, Zou X, et al. Annual report on status of cancer in China, 2010. Chin J Cancer Res = Chung-kuo yen cheng yen chiu. 2014;26:48–58.PubMed
7.
Zurück zum Zitat El-Serag HB, Marrero JA, Rudolph L, Reddy KR. Diagnosis and treatment of hepatocellular carcinoma. Gastroenterology. 2008;134:1752–63.PubMed El-Serag HB, Marrero JA, Rudolph L, Reddy KR. Diagnosis and treatment of hepatocellular carcinoma. Gastroenterology. 2008;134:1752–63.PubMed
8.
Zurück zum Zitat Houtkooper RH, Pirinen E, Auwerx J. Sirtuins as regulators of metabolism and healthspan. Nat Rev Mol Cell Biol. 2012;13:225–38.PubMedPubMedCentral Houtkooper RH, Pirinen E, Auwerx J. Sirtuins as regulators of metabolism and healthspan. Nat Rev Mol Cell Biol. 2012;13:225–38.PubMedPubMedCentral
9.
Zurück zum Zitat Imai S, Armstrong CM, Kaeberlein M, Guarente L. Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase. Nature. 2000;403:795–800.PubMed Imai S, Armstrong CM, Kaeberlein M, Guarente L. Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase. Nature. 2000;403:795–800.PubMed
10.
Zurück zum Zitat Rine J, Herskowitz I. Four genes responsible for a position effect on expression from HML and HMR in saccharomyces cerevisiae. Genetics. 1987;116:9–22.PubMedPubMedCentral Rine J, Herskowitz I. Four genes responsible for a position effect on expression from HML and HMR in saccharomyces cerevisiae. Genetics. 1987;116:9–22.PubMedPubMedCentral
11.
Zurück zum Zitat Gottlieb S, Esposito RE. A new role for a yeast transcriptional silencer gene, SIR2, in regulation of recombination in ribosomal DNA. Cell. 1989;56:771–6.PubMed Gottlieb S, Esposito RE. A new role for a yeast transcriptional silencer gene, SIR2, in regulation of recombination in ribosomal DNA. Cell. 1989;56:771–6.PubMed
12.
Zurück zum Zitat Liang Z, Yang Y, Wang H, Yi W, Yan X, Yan J, et al. Inhibition of SIRT1 signaling sensitizes the antitumor activity of silybin against human lung adenocarcinoma cells in vitro and in vivo. Mol Cancer Ther. 2014;13:1860–72.PubMed Liang Z, Yang Y, Wang H, Yi W, Yan X, Yan J, et al. Inhibition of SIRT1 signaling sensitizes the antitumor activity of silybin against human lung adenocarcinoma cells in vitro and in vivo. Mol Cancer Ther. 2014;13:1860–72.PubMed
13.
Zurück zum Zitat Holloway KR, Barbieri A, Malyarchuk S, Saxena M, Nedeljkovic-Kurepa A, Cameron Mehl M, et al. SIRT1 positively regulates breast cancer associated human aromatase (CYP19A1) expression. Mol Endocrinol. 2013;27:480–90.PubMedPubMedCentral Holloway KR, Barbieri A, Malyarchuk S, Saxena M, Nedeljkovic-Kurepa A, Cameron Mehl M, et al. SIRT1 positively regulates breast cancer associated human aromatase (CYP19A1) expression. Mol Endocrinol. 2013;27:480–90.PubMedPubMedCentral
14.
Zurück zum Zitat Byles V, Zhu L, Lovaas JD, Chmilewski LK, Wang J, Faller DV, et al. SIRT1 induces EMT by cooperating with EMT transcription factors and enhances prostate cancer cell migration and metastasis. Oncogene. 2012;31:4619–29.PubMedPubMedCentral Byles V, Zhu L, Lovaas JD, Chmilewski LK, Wang J, Faller DV, et al. SIRT1 induces EMT by cooperating with EMT transcription factors and enhances prostate cancer cell migration and metastasis. Oncogene. 2012;31:4619–29.PubMedPubMedCentral
15.
Zurück zum Zitat Zhang L, Wang X, Chen P. MiR-204 down regulates SIRT1 and reverts Sirt1-induced epithelial-mesenchymal transition, anoikis resistance and invasion in gastric cancer cells. BMC Cancer. 2013;13:290.PubMedPubMedCentral Zhang L, Wang X, Chen P. MiR-204 down regulates SIRT1 and reverts Sirt1-induced epithelial-mesenchymal transition, anoikis resistance and invasion in gastric cancer cells. BMC Cancer. 2013;13:290.PubMedPubMedCentral
16.
Zurück zum Zitat Han L, Liang XH, Chen LX, Bao SM, Yan ZQ. Sirt1 is highly expressed in brain metastasis tissues of non-small cell lung cancer (NSCLC) and in positive regulation of NSCLC cell migration. Int J Clin Exp Pathol. 2013;6:2357–65.PubMedPubMedCentral Han L, Liang XH, Chen LX, Bao SM, Yan ZQ. Sirt1 is highly expressed in brain metastasis tissues of non-small cell lung cancer (NSCLC) and in positive regulation of NSCLC cell migration. Int J Clin Exp Pathol. 2013;6:2357–65.PubMedPubMedCentral
17.
Zurück zum Zitat Chen W, Bhatia R. Roles of SIRT1 in leukemogenesis. Curr Opin Hematol. 2013;20:308–13.PubMed Chen W, Bhatia R. Roles of SIRT1 in leukemogenesis. Curr Opin Hematol. 2013;20:308–13.PubMed
18.
Zurück zum Zitat Wilking MJ, Singh C, Nihal M, Zhong W, Ahmad N. SIRT1 deacetylase is overexpressed in human melanoma and its small molecule inhibition imparts anti-proliferative response via p53 activation. Arch Biochem Biophys. 2014;563:94–100.PubMedPubMedCentral Wilking MJ, Singh C, Nihal M, Zhong W, Ahmad N. SIRT1 deacetylase is overexpressed in human melanoma and its small molecule inhibition imparts anti-proliferative response via p53 activation. Arch Biochem Biophys. 2014;563:94–100.PubMedPubMedCentral
19.
Zurück zum Zitat Wang H, Liu H, Chen K, Xiao J, He K, Zhang J, et al. SIRT1 promotes tumorigenesis of hepatocellular carcinoma through PI3K/PTEN/AKT signaling. Oncol Rep. 2012;28:311–8.PubMed Wang H, Liu H, Chen K, Xiao J, He K, Zhang J, et al. SIRT1 promotes tumorigenesis of hepatocellular carcinoma through PI3K/PTEN/AKT signaling. Oncol Rep. 2012;28:311–8.PubMed
20.
Zurück zum Zitat Curtil C, Enache LS, Radreau P, Dron AG, Scholtes C, Deloire A, et al. The metabolic sensors FXRα, PGC1-α, and SIRT1 cooperatively regulate hepatitis B virus transcription. FASEB J: Off Publ Fed Am Soc Exp Biol. 2014;28:1454–63. Curtil C, Enache LS, Radreau P, Dron AG, Scholtes C, Deloire A, et al. The metabolic sensors FXRα, PGC1-α, and SIRT1 cooperatively regulate hepatitis B virus transcription. FASEB J: Off Publ Fed Am Soc Exp Biol. 2014;28:1454–63.
21.
Zurück zum Zitat Min J, Landry J, Sternglanz R, Xu RM. Crystal structure of a SIR2 homolog-NAD complex. Cell. 2001;105:269–79.PubMed Min J, Landry J, Sternglanz R, Xu RM. Crystal structure of a SIR2 homolog-NAD complex. Cell. 2001;105:269–79.PubMed
22.
Zurück zum Zitat Finnin MS, Donigian JR, Pavletich NP. Structure of the histone deacetylase SIRT2. Nat Struct Biol. 2001;8:621–5.PubMed Finnin MS, Donigian JR, Pavletich NP. Structure of the histone deacetylase SIRT2. Nat Struct Biol. 2001;8:621–5.PubMed
23.
24.
Zurück zum Zitat Chakrabarty SP, Balaram H. Reversible binding of zinc in plasmodium falciparum SIR2: structure and activity of the apoenzyme. Biochim Biophys Acta. 1804;2010:1743–50. Chakrabarty SP, Balaram H. Reversible binding of zinc in plasmodium falciparum SIR2: structure and activity of the apoenzyme. Biochim Biophys Acta. 1804;2010:1743–50.
25.
Zurück zum Zitat Avalos JL, Boeke JD, Wolberger C. Structural basis for the mechanism and regulation of Sir2 enzymes. Mol Cell. 2004;13:639–48.PubMed Avalos JL, Boeke JD, Wolberger C. Structural basis for the mechanism and regulation of Sir2 enzymes. Mol Cell. 2004;13:639–48.PubMed
26.
Zurück zum Zitat Sanders BD, Zhao K, Slama JT, Marmorstein R. Structural basis for nicotinamide inhibition and base exchange in Sir2 enzymes. Mol Cell. 2007;25:463–72.PubMedPubMedCentral Sanders BD, Zhao K, Slama JT, Marmorstein R. Structural basis for nicotinamide inhibition and base exchange in Sir2 enzymes. Mol Cell. 2007;25:463–72.PubMedPubMedCentral
27.
Zurück zum Zitat Zhao K, Harshaw R, Chai X, Marmorstein R. Structural basis for nicotinamide cleavage and ADP-ribose transfer by NAD(+)-dependent Sir2 histone/protein deacetylases. Proc Natl Acad Sci U S A. 2004;101:8563–8.PubMedPubMedCentral Zhao K, Harshaw R, Chai X, Marmorstein R. Structural basis for nicotinamide cleavage and ADP-ribose transfer by NAD(+)-dependent Sir2 histone/protein deacetylases. Proc Natl Acad Sci U S A. 2004;101:8563–8.PubMedPubMedCentral
28.
Zurück zum Zitat Magni G, Amici A, Emanuelli M, Orsomando G, Raffaelli N, Ruggieri S. Structure and function of nicotinamide mononucleotide adenylyltransferase. Curr Med Chem. 2004;11:873–85.PubMed Magni G, Amici A, Emanuelli M, Orsomando G, Raffaelli N, Ruggieri S. Structure and function of nicotinamide mononucleotide adenylyltransferase. Curr Med Chem. 2004;11:873–85.PubMed
29.
Zurück zum Zitat van den Berghe G. The role of the liver in metabolic homeostasis: implications for inborn errors of metabolism. J Inherit Metab Dis. 1991;14:407–20.PubMed van den Berghe G. The role of the liver in metabolic homeostasis: implications for inborn errors of metabolism. J Inherit Metab Dis. 1991;14:407–20.PubMed
30.
Zurück zum Zitat Chang HC, Guarente L. SIRT1 and other sirtuins in metabolism. Trends endocrinol Metab: TEM. 2014;25:138–45.PubMed Chang HC, Guarente L. SIRT1 and other sirtuins in metabolism. Trends endocrinol Metab: TEM. 2014;25:138–45.PubMed
31.
Zurück zum Zitat Rodgers JT, Lerin C, Haas W, Gygi SP, Spiegelman BM, Puigserver P. Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1. Nature. 2005;434:113–8.PubMed Rodgers JT, Lerin C, Haas W, Gygi SP, Spiegelman BM, Puigserver P. Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1. Nature. 2005;434:113–8.PubMed
32.
Zurück zum Zitat Liu Y, Dentin R, Chen D, Hedrick S, Ravnskjaer K, Schenk S, et al. A fasting inducible switch modulates gluconeogenesis via activator/coactivator exchange. Nature. 2008;456:269–73.PubMedPubMedCentral Liu Y, Dentin R, Chen D, Hedrick S, Ravnskjaer K, Schenk S, et al. A fasting inducible switch modulates gluconeogenesis via activator/coactivator exchange. Nature. 2008;456:269–73.PubMedPubMedCentral
33.
Zurück zum Zitat Purushotham A, Schug TT, Xu Q, Surapureddi S, Guo X, Li X. Hepatocyte-specific deletion of SIRT1 alters fatty acid metabolism and results in hepatic steatosis and inflammation. Cell Metab. 2009;9:327–38.PubMedPubMedCentral Purushotham A, Schug TT, Xu Q, Surapureddi S, Guo X, Li X. Hepatocyte-specific deletion of SIRT1 alters fatty acid metabolism and results in hepatic steatosis and inflammation. Cell Metab. 2009;9:327–38.PubMedPubMedCentral
34.
Zurück zum Zitat Yin H, Hu M, Liang X, Ajmo JM, Li X, Bataller R, et al. Deletion of SIRT1 from hepatocytes in mice disrupts lipin-1 signaling and aggravates alcoholic fatty liver. Gastroenterology. 2014;146:801–11.PubMed Yin H, Hu M, Liang X, Ajmo JM, Li X, Bataller R, et al. Deletion of SIRT1 from hepatocytes in mice disrupts lipin-1 signaling and aggravates alcoholic fatty liver. Gastroenterology. 2014;146:801–11.PubMed
35.
Zurück zum Zitat Li Y, Xu S, Giles A, Nakamura K, Lee JW, Hou X, et al. Hepatic overexpression of SIRT1 in mice attenuates endoplasmic reticulum stress and insulin resistance in the liver. FASEB J: Off Publ Fed Am Soc Exp Biol. 2011;25:1664–79. Li Y, Xu S, Giles A, Nakamura K, Lee JW, Hou X, et al. Hepatic overexpression of SIRT1 in mice attenuates endoplasmic reticulum stress and insulin resistance in the liver. FASEB J: Off Publ Fed Am Soc Exp Biol. 2011;25:1664–79.
36.
Zurück zum Zitat Walker AK, Yang F, Jiang K, Ji JY, Watts JL, Purushotham A, et al. Conserved role of SIRT1 orthologs in fasting-dependent inhibition of the lipid/cholesterol regulator SREBP. Genes Dev. 2010;24:1403–17.PubMedPubMedCentral Walker AK, Yang F, Jiang K, Ji JY, Watts JL, Purushotham A, et al. Conserved role of SIRT1 orthologs in fasting-dependent inhibition of the lipid/cholesterol regulator SREBP. Genes Dev. 2010;24:1403–17.PubMedPubMedCentral
37.
Zurück zum Zitat Li X, Zhang S, Blander G, Tse JG, Krieger M, Guarente L. SIRT1 deacetylates and positively regulates the nuclear receptor LXR. Mol Cell. 2007;28:91–106.PubMed Li X, Zhang S, Blander G, Tse JG, Krieger M, Guarente L. SIRT1 deacetylates and positively regulates the nuclear receptor LXR. Mol Cell. 2007;28:91–106.PubMed
38.
Zurück zum Zitat Kemper JK, Xiao Z, Ponugoti B, Miao J, Fang S, Kanamaluru D, et al. FXR acetylation is normally dynamically regulated by p300 and SIRT1 but constitutively elevated in metabolic disease states. Cell Metab. 2009;10:392–404.PubMedPubMedCentral Kemper JK, Xiao Z, Ponugoti B, Miao J, Fang S, Kanamaluru D, et al. FXR acetylation is normally dynamically regulated by p300 and SIRT1 but constitutively elevated in metabolic disease states. Cell Metab. 2009;10:392–404.PubMedPubMedCentral
39.
Zurück zum Zitat Purushotham A, Xu Q, Lu J, Foley JF, Yan X, Kim DH, et al. Hepatic deletion of SIRT1 decreases hepatocyte nuclear factor 1alpha/farnesoid X receptor signaling and induces formation of cholesterol gallstones in mice. Mol Cell Biol. 2012;32:1226–36.PubMedPubMedCentral Purushotham A, Xu Q, Lu J, Foley JF, Yan X, Kim DH, et al. Hepatic deletion of SIRT1 decreases hepatocyte nuclear factor 1alpha/farnesoid X receptor signaling and induces formation of cholesterol gallstones in mice. Mol Cell Biol. 2012;32:1226–36.PubMedPubMedCentral
40.
Zurück zum Zitat Asher G, Gatfield D, Stratmann M, Reinke H, Dibner C, Kreppel F, et al. SIRT1 regulates circadian clock gene expression through PER2 deacetylation. Cell. 2008;134:317–28.PubMed Asher G, Gatfield D, Stratmann M, Reinke H, Dibner C, Kreppel F, et al. SIRT1 regulates circadian clock gene expression through PER2 deacetylation. Cell. 2008;134:317–28.PubMed
41.
Zurück zum Zitat Nakahata Y, Kaluzova M, Grimaldi B, Sahar S, Hirayama J, Chen D, et al. The NAD+-dependent deacetylase SIRT1 modulates CLOCK-mediated chromatin remodeling and circadian control. Cell. 2008;134:329–40.PubMedPubMedCentral Nakahata Y, Kaluzova M, Grimaldi B, Sahar S, Hirayama J, Chen D, et al. The NAD+-dependent deacetylase SIRT1 modulates CLOCK-mediated chromatin remodeling and circadian control. Cell. 2008;134:329–40.PubMedPubMedCentral
42.
Zurück zum Zitat Bellet MM, Nakahata Y, Boudjelal M, Watts E, Mossakowska DE, Edwards KA, et al. Pharmacological modulation of circadian rhythms by synthetic activators of the deacetylase SIRT1. Proc Natl Acad Sci U S A. 2013;110:3333–8.PubMedPubMedCentral Bellet MM, Nakahata Y, Boudjelal M, Watts E, Mossakowska DE, Edwards KA, et al. Pharmacological modulation of circadian rhythms by synthetic activators of the deacetylase SIRT1. Proc Natl Acad Sci U S A. 2013;110:3333–8.PubMedPubMedCentral
43.
Zurück zum Zitat Simone PortmannChen J, Zhang B, Wong N, Lo AW, To KF, Chan AW, et al. Sirtuin 1 is upregulated in a subset of hepatocellular carcinomas where it is essential for telomere maintenance and tumor cell growth. Cancer Res. 2011;71:4138–49. Simone PortmannChen J, Zhang B, Wong N, Lo AW, To KF, Chan AW, et al. Sirtuin 1 is upregulated in a subset of hepatocellular carcinomas where it is essential for telomere maintenance and tumor cell growth. Cancer Res. 2011;71:4138–49.
44.
Zurück zum Zitat Portmann S, Fahrner R, Lechleiter A, Keogh A, Overney S, Laemmle A, et al. Antitumor effect of SIRT1 inhibition in human HCC tumor models in vitro and in vivo. Mol Cancer Ther. 2013;12:499–508.PubMed Portmann S, Fahrner R, Lechleiter A, Keogh A, Overney S, Laemmle A, et al. Antitumor effect of SIRT1 inhibition in human HCC tumor models in vitro and in vivo. Mol Cancer Ther. 2013;12:499–508.PubMed
45.
Zurück zum Zitat Chen HC, Jeng YM, Yuan RH, Hsu HC, Chen YL. SIRT1 promotes tumorigenesis and resistance to chemotherapy in hepatocellular carcinoma and its expression predicts poor prognosis. Ann Surg Oncol. 2012;19:2011–9.PubMed Chen HC, Jeng YM, Yuan RH, Hsu HC, Chen YL. SIRT1 promotes tumorigenesis and resistance to chemotherapy in hepatocellular carcinoma and its expression predicts poor prognosis. Ann Surg Oncol. 2012;19:2011–9.PubMed
46.
Zurück zum Zitat Choi HN, Bae JS, Jamiyandorj U, Noh SJ, Park HS, Jang KY, et al. Expression and role of SIRT1 in hepatocellular carcinoma. Oncol Rep. 2011;26:503–10.PubMed Choi HN, Bae JS, Jamiyandorj U, Noh SJ, Park HS, Jang KY, et al. Expression and role of SIRT1 in hepatocellular carcinoma. Oncol Rep. 2011;26:503–10.PubMed
47.
Zurück zum Zitat Bae HJ, Noh JH, Kim JK, Eun JW, Jung KH, Kim MG, et al. MicroRNA-29c functions as a tumor suppressor by direct targeting oncogenic SIRT1 in hepatocellular carcinoma. Oncogene. 2014;33:2557–67.PubMed Bae HJ, Noh JH, Kim JK, Eun JW, Jung KH, Kim MG, et al. MicroRNA-29c functions as a tumor suppressor by direct targeting oncogenic SIRT1 in hepatocellular carcinoma. Oncogene. 2014;33:2557–67.PubMed
48.
Zurück zum Zitat Hao C, Zhu P, Yang X, Han Z, Jiang J, Zong C, et al. Overexpression of SIRT1 promotes metastasis through epithelial-mesenchymal transition in hepatocellular carcinoma. BMC Cancer. 2014;14:978.PubMedPubMedCentral Hao C, Zhu P, Yang X, Han Z, Jiang J, Zong C, et al. Overexpression of SIRT1 promotes metastasis through epithelial-mesenchymal transition in hepatocellular carcinoma. BMC Cancer. 2014;14:978.PubMedPubMedCentral
49.
Zurück zum Zitat Ding W, You H, Dang H, LeBlanc F, Galicia V, Lu SC, et al. Epithelial-to-mesenchymal transition of murine liver tumor cells promotes invasion. Hepatology. 2010;52:945–53.PubMedPubMedCentral Ding W, You H, Dang H, LeBlanc F, Galicia V, Lu SC, et al. Epithelial-to-mesenchymal transition of murine liver tumor cells promotes invasion. Hepatology. 2010;52:945–53.PubMedPubMedCentral
50.
Zurück zum Zitat Liang XJ, Finkel T, Shen DW, Yin JJ, Aszalos A, Gottesman MM. SIRT1 contributes in part to cisplatin resistance in cancer cells by altering mitochondrial metabolism. Mol Cancer Res: MCR. 2008;6:1499–506.PubMedPubMedCentral Liang XJ, Finkel T, Shen DW, Yin JJ, Aszalos A, Gottesman MM. SIRT1 contributes in part to cisplatin resistance in cancer cells by altering mitochondrial metabolism. Mol Cancer Res: MCR. 2008;6:1499–506.PubMedPubMedCentral
51.
Zurück zum Zitat Lowinger TB, Riedl B, Dumas J, Smith RA. Design and discovery of small molecules targeting raf-1 kinase. Curr Pharm Des. 2002;8:2269–78.PubMed Lowinger TB, Riedl B, Dumas J, Smith RA. Design and discovery of small molecules targeting raf-1 kinase. Curr Pharm Des. 2002;8:2269–78.PubMed
52.
Zurück zum Zitat Mann A, Breuhahn K, Schirmacher P, Wilhelmi A, Beyer C, Rosenau A, et al. Up- and down-regulation of granulocyte/macrophage-colony stimulating factor activity in murine skin increase susceptibility to skin carcinogenesis by independent mechanisms. Cancer Res. 2001;61:2311–9.PubMed Mann A, Breuhahn K, Schirmacher P, Wilhelmi A, Beyer C, Rosenau A, et al. Up- and down-regulation of granulocyte/macrophage-colony stimulating factor activity in murine skin increase susceptibility to skin carcinogenesis by independent mechanisms. Cancer Res. 2001;61:2311–9.PubMed
53.
Zurück zum Zitat Wilhelm S, Carter C, Lynch M, Lowinger T, Dumas J, Smith RA, et al. Discovery and development of sorafenib: a multikinase inhibitor for treating cancer. Nat Rev Drug Discov. 2006;5:835–44.PubMed Wilhelm S, Carter C, Lynch M, Lowinger T, Dumas J, Smith RA, et al. Discovery and development of sorafenib: a multikinase inhibitor for treating cancer. Nat Rev Drug Discov. 2006;5:835–44.PubMed
54.
Zurück zum Zitat Gores GJ. Decade in review-hepatocellular carcinoma: HCC-subtypes, stratification and sorafenib. Nat Rev Gastroenterol Hepatol. 2014;11:645–7.PubMed Gores GJ. Decade in review-hepatocellular carcinoma: HCC-subtypes, stratification and sorafenib. Nat Rev Gastroenterol Hepatol. 2014;11:645–7.PubMed
55.
Zurück zum Zitat Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359:378–90.PubMed Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359:378–90.PubMed
56.
Zurück zum Zitat Yau T, Chan P, Ng KK, Chok SH, Cheung TT, Fan ST, et al. Phase 2 open-label study of single-agent sorafenib in treating advanced hepatocellular carcinoma in a hepatitis B-endemic Asian population: presence of lung metastasis predicts poor response. Cancer. 2009;115:428–36.PubMed Yau T, Chan P, Ng KK, Chok SH, Cheung TT, Fan ST, et al. Phase 2 open-label study of single-agent sorafenib in treating advanced hepatocellular carcinoma in a hepatitis B-endemic Asian population: presence of lung metastasis predicts poor response. Cancer. 2009;115:428–36.PubMed
57.
Zurück zum Zitat Abou-Alfa GK, Amadori D, Santoro A, Figer A, De Greve J, Lathia C, et al. Safety and efficacy of sorafenib in patients with hepatocellular carcinoma (HCC) and Child-Pugh A versus B cirrhosis. Gastrointest Cancer Res: GCR. 2011;4:40–4.PubMedPubMedCentral Abou-Alfa GK, Amadori D, Santoro A, Figer A, De Greve J, Lathia C, et al. Safety and efficacy of sorafenib in patients with hepatocellular carcinoma (HCC) and Child-Pugh A versus B cirrhosis. Gastrointest Cancer Res: GCR. 2011;4:40–4.PubMedPubMedCentral
58.
Zurück zum Zitat Xie Y, Zhang J, Ye S, He M, Ren R, Yuan D, et al. SirT1 regulates radiosensitivity of hepatoma cells differently under normoxic and hypoxic conditions. Cancer Sci. 2012;103:1238–44.PubMed Xie Y, Zhang J, Ye S, He M, Ren R, Yuan D, et al. SirT1 regulates radiosensitivity of hepatoma cells differently under normoxic and hypoxic conditions. Cancer Sci. 2012;103:1238–44.PubMed
59.
Zurück zum Zitat Hu Y, Wang S, Wu X, Zhang J, Chen R, Chen M, et al. Chinese herbal medicine-derived compounds for cancer therapy: a focus on hepatocellular carcinoma. J Ethnopharmacol. 2013;149:601–12.PubMed Hu Y, Wang S, Wu X, Zhang J, Chen R, Chen M, et al. Chinese herbal medicine-derived compounds for cancer therapy: a focus on hepatocellular carcinoma. J Ethnopharmacol. 2013;149:601–12.PubMed
60.
Zurück zum Zitat Lin HC, Chen YF, Hsu WH, Yang CW, Kao CH, Tsai TF. Resveratrol helps recovery from fatty liver and protects against hepatocellular carcinoma induced by hepatitis B virus X protein in a mouse model. Cancer Prev Res. 2012;5:952–62. Lin HC, Chen YF, Hsu WH, Yang CW, Kao CH, Tsai TF. Resveratrol helps recovery from fatty liver and protects against hepatocellular carcinoma induced by hepatitis B virus X protein in a mouse model. Cancer Prev Res. 2012;5:952–62.
61.
Zurück zum Zitat Ajmo JM, Liang X, Rogers CQ, Pennock B, You M. Resveratrol alleviates alcoholic fatty liver in mice. Am J Physiol Gastrointest Liver Physiol. 2008;295:G833–42.PubMedPubMedCentral Ajmo JM, Liang X, Rogers CQ, Pennock B, You M. Resveratrol alleviates alcoholic fatty liver in mice. Am J Physiol Gastrointest Liver Physiol. 2008;295:G833–42.PubMedPubMedCentral
62.
Zurück zum Zitat Kim DH, Jung YJ, Lee JE, Lee AS, Kang KP, Lee S, et al. SIRT1 activation by resveratrol ameliorates cisplatin-induced renal injury through deacetylation of p53. Am J Physiol Renal Physiol. 2011;301:F427–35.PubMed Kim DH, Jung YJ, Lee JE, Lee AS, Kang KP, Lee S, et al. SIRT1 activation by resveratrol ameliorates cisplatin-induced renal injury through deacetylation of p53. Am J Physiol Renal Physiol. 2011;301:F427–35.PubMed
63.
Zurück zum Zitat Bishayee A, Politis T, Darvesh AS. Resveratrol in the chemoprevention and treatment of hepatocellular carcinoma. Cancer Treat Rev. 2010;36:43–53.PubMed Bishayee A, Politis T, Darvesh AS. Resveratrol in the chemoprevention and treatment of hepatocellular carcinoma. Cancer Treat Rev. 2010;36:43–53.PubMed
64.
Zurück zum Zitat Rajasekaran D, Elavarasan J, Sivalingam M, Ganapathy E, Kumar A, Kalpana K, et al. Resveratrol interferes with N-nitrosodiethylamine-induced hepatocellular carcinoma at early and advanced stages in male Wistar rats. Mol Med Rep. 2011;4:1211–7.PubMed Rajasekaran D, Elavarasan J, Sivalingam M, Ganapathy E, Kumar A, Kalpana K, et al. Resveratrol interferes with N-nitrosodiethylamine-induced hepatocellular carcinoma at early and advanced stages in male Wistar rats. Mol Med Rep. 2011;4:1211–7.PubMed
65.
Zurück zum Zitat Kozuki Y, Miura Y, Yagasaki K. Resveratrol suppresses hepatoma cell invasion independently of its anti-proliferative action. Cancer Lett. 2001;167:151–6.PubMed Kozuki Y, Miura Y, Yagasaki K. Resveratrol suppresses hepatoma cell invasion independently of its anti-proliferative action. Cancer Lett. 2001;167:151–6.PubMed
66.
Zurück zum Zitat Yeh CB, Hsieh MJ, Lin CW, Chiou HL, Lin PY, Chen TY, et al. The antimetastatic effects of resveratrol on hepatocellular carcinoma through the downregulation of a metastasis-associated protease by SP-1 modulation. PLoS One. 2013;8, e56661.PubMedPubMedCentral Yeh CB, Hsieh MJ, Lin CW, Chiou HL, Lin PY, Chen TY, et al. The antimetastatic effects of resveratrol on hepatocellular carcinoma through the downregulation of a metastasis-associated protease by SP-1 modulation. PLoS One. 2013;8, e56661.PubMedPubMedCentral
67.
Zurück zum Zitat Kuo PL, Chiang LC, Lin CC. Resveratrol- induced apoptosis is mediated by p53-dependent pathway in Hep G2 cells. Life Sci. 2002;72:23–34.PubMed Kuo PL, Chiang LC, Lin CC. Resveratrol- induced apoptosis is mediated by p53-dependent pathway in Hep G2 cells. Life Sci. 2002;72:23–34.PubMed
68.
Zurück zum Zitat Huang C, Ma WY, Goranson A, Dong Z. Resveratrol suppresses cell transformation and induces apoptosis through a p53-dependent pathway. Carcinogenesis. 1999;20:237–42.PubMed Huang C, Ma WY, Goranson A, Dong Z. Resveratrol suppresses cell transformation and induces apoptosis through a p53-dependent pathway. Carcinogenesis. 1999;20:237–42.PubMed
69.
Zurück zum Zitat Shih A, Davis FB, Lin HY, Davis PJ. Resveratrol induces apoptosis in thyroid cancer cell lines via a MAPK- and p53-dependent mechanism. J Clin Endocrinol Metab. 2002;87:1223–32.PubMed Shih A, Davis FB, Lin HY, Davis PJ. Resveratrol induces apoptosis in thyroid cancer cell lines via a MAPK- and p53-dependent mechanism. J Clin Endocrinol Metab. 2002;87:1223–32.PubMed
70.
Zurück zum Zitat Beher D, Wu J, Cumine S, Kim KW, Lu SC, Atangan L, et al. Resveratrol is not a direct activator of SIRT1 enzyme activity. Chem Biol Drug Des. 2009;74:619–24.PubMed Beher D, Wu J, Cumine S, Kim KW, Lu SC, Atangan L, et al. Resveratrol is not a direct activator of SIRT1 enzyme activity. Chem Biol Drug Des. 2009;74:619–24.PubMed
71.
Zurück zum Zitat Borra MT, Smith BC, Denu JM. Mechanism of human SIRT1 activation by resveratrol. J Biol Chem. 2005;280:17187–95.PubMed Borra MT, Smith BC, Denu JM. Mechanism of human SIRT1 activation by resveratrol. J Biol Chem. 2005;280:17187–95.PubMed
72.
Zurück zum Zitat Kaeberlein M, McDonagh T, Heltweg B, Hixon J, Westman EA, Caldwell SD, et al. Substrate-specific activation of sirtuins by resveratrol. J Biol Chem. 2005;280:17038–45.PubMed Kaeberlein M, McDonagh T, Heltweg B, Hixon J, Westman EA, Caldwell SD, et al. Substrate-specific activation of sirtuins by resveratrol. J Biol Chem. 2005;280:17038–45.PubMed
73.
Zurück zum Zitat Zschoernig B, Mahlknecht U. Carboxy-terminal phosphorylation of SIRT1 by protein kinase CK2. Biochem Biophys Res Commun. 2009;381:372–7.PubMed Zschoernig B, Mahlknecht U. Carboxy-terminal phosphorylation of SIRT1 by protein kinase CK2. Biochem Biophys Res Commun. 2009;381:372–7.PubMed
74.
Zurück zum Zitat Ahmad KA, Harris NH, Johnson AD, Lindvall HC, Wang G, Ahmed K. Protein kinase CK2 modulates apoptosis induced by resveratrol and epigallocatechin-3-gallate in prostate cancer cells. Mol Cancer Ther. 2007;6:1006–12.PubMed Ahmad KA, Harris NH, Johnson AD, Lindvall HC, Wang G, Ahmed K. Protein kinase CK2 modulates apoptosis induced by resveratrol and epigallocatechin-3-gallate in prostate cancer cells. Mol Cancer Ther. 2007;6:1006–12.PubMed
75.
Zurück zum Zitat Yang Y, Fu W, Chen J, Olashaw N, Zhang X, Nicosia SV, et al. SIRT1 sumoylation regulates its deacetylase activity and cellular response to genotoxic stress. Nat Cell Biol. 2007;9:1253–62.PubMedPubMedCentral Yang Y, Fu W, Chen J, Olashaw N, Zhang X, Nicosia SV, et al. SIRT1 sumoylation regulates its deacetylase activity and cellular response to genotoxic stress. Nat Cell Biol. 2007;9:1253–62.PubMedPubMedCentral
76.
Zurück zum Zitat Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116:281–97.PubMed Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116:281–97.PubMed
77.
Zurück zum Zitat Buurman R, Gurlevik E, Schaffer V, Eilers M, Sandbothe M, Kreipe H, et al. Histone deacetylases activate hepatocyte growth factor signaling by repressing microRNA-449 in hepatocellular carcinoma cells. Gastroenterology. 2012;143:811–20. e811-815.PubMed Buurman R, Gurlevik E, Schaffer V, Eilers M, Sandbothe M, Kreipe H, et al. Histone deacetylases activate hepatocyte growth factor signaling by repressing microRNA-449 in hepatocellular carcinoma cells. Gastroenterology. 2012;143:811–20. e811-815.PubMed
78.
Zurück zum Zitat Zhang H, Feng Z, Huang R, Xia Z, Xiang G, Zhang J. MicroRNA-449 suppresses proliferation of hepatoma cell lines through blockade lipid metabolic pathway related to SIRT1. Int J Oncol. 2014;45:2143–52.PubMed Zhang H, Feng Z, Huang R, Xia Z, Xiang G, Zhang J. MicroRNA-449 suppresses proliferation of hepatoma cell lines through blockade lipid metabolic pathway related to SIRT1. Int J Oncol. 2014;45:2143–52.PubMed
79.
Zurück zum Zitat Parpart S, Roessler S, Dong F, Rao V, Takai A, Ji J, et al. Modulation of miR-29 expression by α-fetoprotein is linked to the hepatocellular carcinoma epigenome. Hepatology. 2014;60:872–83.PubMedPubMedCentral Parpart S, Roessler S, Dong F, Rao V, Takai A, Ji J, et al. Modulation of miR-29 expression by α-fetoprotein is linked to the hepatocellular carcinoma epigenome. Hepatology. 2014;60:872–83.PubMedPubMedCentral
80.
Zurück zum Zitat Yamashita T, Honda M, Takatori H, Nishino R, Minato H, Takamura H, et al. Activation of lipogenic pathway correlates with cell proliferation and poor prognosis in hepatocellular carcinoma. J Hepatol. 2009;50:100–10.PubMed Yamashita T, Honda M, Takatori H, Nishino R, Minato H, Takamura H, et al. Activation of lipogenic pathway correlates with cell proliferation and poor prognosis in hepatocellular carcinoma. J Hepatol. 2009;50:100–10.PubMed
81.
Zurück zum Zitat Tazawa H, Tsuchiya N, Izumiya M, Nakagama H. Tumor-suppressive miR-34a induces senescence-like growth arrest through modulation of the E2F pathway in human colon cancer cells. Proc Natl Acad Sci U S A. 2007;104:15472–7.PubMedPubMedCentral Tazawa H, Tsuchiya N, Izumiya M, Nakagama H. Tumor-suppressive miR-34a induces senescence-like growth arrest through modulation of the E2F pathway in human colon cancer cells. Proc Natl Acad Sci U S A. 2007;104:15472–7.PubMedPubMedCentral
82.
Zurück zum Zitat Welch C, Chen Y, Stallings RL. MicroRNA-34a functions as a potential tumor suppressor by inducing apoptosis in neuroblastoma cells. Oncogene. 2007;26:5017–22.PubMed Welch C, Chen Y, Stallings RL. MicroRNA-34a functions as a potential tumor suppressor by inducing apoptosis in neuroblastoma cells. Oncogene. 2007;26:5017–22.PubMed
83.
Zurück zum Zitat Lou W, Chen Q, Ma L, Liu J, Yang Z, Shen J, et al. Oncolytic adenovirus co-expressing miRNA-34a and IL-24 induces superior antitumor activity in experimental tumor model. J Mol Med. 2013;91:715–25.PubMed Lou W, Chen Q, Ma L, Liu J, Yang Z, Shen J, et al. Oncolytic adenovirus co-expressing miRNA-34a and IL-24 induces superior antitumor activity in experimental tumor model. J Mol Med. 2013;91:715–25.PubMed
84.
Zurück zum Zitat Lee J, Padhye A, Sharma A, Song G, Miao J, Mo YY, et al. A pathway involving farnesoid X receptor and small heterodimer partner positively regulates hepatic sirtuin 1 levels via microRNA-34a inhibition. J Biol Chem. 2010;285:12604–11.PubMedPubMedCentral Lee J, Padhye A, Sharma A, Song G, Miao J, Mo YY, et al. A pathway involving farnesoid X receptor and small heterodimer partner positively regulates hepatic sirtuin 1 levels via microRNA-34a inhibition. J Biol Chem. 2010;285:12604–11.PubMedPubMedCentral
85.
Zurück zum Zitat Choi SE, Fu T, Seok S, Kim DH, Yu E, Lee KW, et al. Elevated microRNA-34a in obesity reduces NAD+ levels and SIRT1 activity by directly targeting NAMPT. Aging Cell. 2013;12:1062–72.PubMed Choi SE, Fu T, Seok S, Kim DH, Yu E, Lee KW, et al. Elevated microRNA-34a in obesity reduces NAD+ levels and SIRT1 activity by directly targeting NAMPT. Aging Cell. 2013;12:1062–72.PubMed
86.
Zurück zum Zitat Duarte MS, Castro RE, Ferreira DM, Afonso MB, Borralho PM, Machado MV, et al. miR-34a/SIRT1/p53 is suppressed by ursodeoxycholic acid in the rat liver and activated by disease severity in human non-alcoholic fatty liver disease. J Hepatol. 2013;58:119–25. Duarte MS, Castro RE, Ferreira DM, Afonso MB, Borralho PM, Machado MV, et al. miR-34a/SIRT1/p53 is suppressed by ursodeoxycholic acid in the rat liver and activated by disease severity in human non-alcoholic fatty liver disease. J Hepatol. 2013;58:119–25.
87.
Zurück zum Zitat Ferreira DM, Afonso MB, Rodrigues PM, Simao AL, Pereira DM, Borralho PM, et al. c-Jun N-terminal kinase 1/c-Jun activation of the p53/microRNA 34a/sirtuin 1 pathway contributes to apoptosis induced by deoxycholic acid in rat liver. Mol Cell Biol. 2014;34:1100–20.PubMedPubMedCentral Ferreira DM, Afonso MB, Rodrigues PM, Simao AL, Pereira DM, Borralho PM, et al. c-Jun N-terminal kinase 1/c-Jun activation of the p53/microRNA 34a/sirtuin 1 pathway contributes to apoptosis induced by deoxycholic acid in rat liver. Mol Cell Biol. 2014;34:1100–20.PubMedPubMedCentral
88.
Zurück zum Zitat Yin H, Hu M, Zhang R, Shen Z, Flatow L, You M. microRNA-217 promotes ethanol-induced fat accumulation in hepatocytes by down-regulating SIRT1. J Biol Chem. 2012;287:9817–26.PubMedPubMedCentral Yin H, Hu M, Zhang R, Shen Z, Flatow L, You M. microRNA-217 promotes ethanol-induced fat accumulation in hepatocytes by down-regulating SIRT1. J Biol Chem. 2012;287:9817–26.PubMedPubMedCentral
89.
Zurück zum Zitat Eades G, Yao Y, Yang M, Zhang Y, Chumsri S, Zhou Q. miR-200a regulates SIRT1 expression and epithelial to mesenchymal transition (EMT)-like transformation in mammary epithelial cells. J Biol Chem. 2011;286:25992–6002.PubMedPubMedCentral Eades G, Yao Y, Yang M, Zhang Y, Chumsri S, Zhou Q. miR-200a regulates SIRT1 expression and epithelial to mesenchymal transition (EMT)-like transformation in mammary epithelial cells. J Biol Chem. 2011;286:25992–6002.PubMedPubMedCentral
90.
Zurück zum Zitat Streissguth AP, Bookstein FL, Barr HM, Sampson PD, O’Malley K, Young JK. Risk factors for adverse life outcomes in fetal alcohol syndrome and fetal alcohol effects. J Dev Behav Pediatr: JDBP. 2004;25:228–38.PubMed Streissguth AP, Bookstein FL, Barr HM, Sampson PD, O’Malley K, Young JK. Risk factors for adverse life outcomes in fetal alcohol syndrome and fetal alcohol effects. J Dev Behav Pediatr: JDBP. 2004;25:228–38.PubMed
91.
Zurück zum Zitat Thompson KJ, Humphries JR, Niemeyer DJ, Sindram D, McKillop IH. The effect of alcohol on Sirt1 expression and function in animal and human models of hepatocellular carcinoma (HCC). Adv Exp Med Biol. 2015;815:361–73.PubMed Thompson KJ, Humphries JR, Niemeyer DJ, Sindram D, McKillop IH. The effect of alcohol on Sirt1 expression and function in animal and human models of hepatocellular carcinoma (HCC). Adv Exp Med Biol. 2015;815:361–73.PubMed
92.
Zurück zum Zitat Zhang YY, Zhou LM. Omentin-1, a new adipokine, promotes apoptosis through regulating Sirt1-dependent p53 deacetylation in hepatocellular carcinoma cells. Eur J Pharmacol. 2013;698:137–44.PubMed Zhang YY, Zhou LM. Omentin-1, a new adipokine, promotes apoptosis through regulating Sirt1-dependent p53 deacetylation in hepatocellular carcinoma cells. Eur J Pharmacol. 2013;698:137–44.PubMed
93.
Zurück zum Zitat Vogelstein B, Lane D, Levine AJ. Surfing the p53 network. Nature. 2000;408:307–10.PubMed Vogelstein B, Lane D, Levine AJ. Surfing the p53 network. Nature. 2000;408:307–10.PubMed
94.
Zurück zum Zitat Levine AJ, Finlay CA, Hinds PW. p53 is a tumor suppressor gene. Cell. 2004;116:S67–9. 61 p following S69.PubMed Levine AJ, Finlay CA, Hinds PW. p53 is a tumor suppressor gene. Cell. 2004;116:S67–9. 61 p following S69.PubMed
95.
Zurück zum Zitat Gu W, Roeder RG. Activation of p53 sequence-specific DNA binding by acetylation of the p53 C-terminal domain. Cell. 1997;90:595–606.PubMed Gu W, Roeder RG. Activation of p53 sequence-specific DNA binding by acetylation of the p53 C-terminal domain. Cell. 1997;90:595–606.PubMed
96.
97.
Zurück zum Zitat Vaziri H, Dessain SK, Ng Eaton E, Imai SI, Frye RA, Pandita TK, et al. hSIR2(SIRT1) functions as an NAD-dependent p53 deacetylase. Cell. 2001;107:149–59.PubMed Vaziri H, Dessain SK, Ng Eaton E, Imai SI, Frye RA, Pandita TK, et al. hSIR2(SIRT1) functions as an NAD-dependent p53 deacetylase. Cell. 2001;107:149–59.PubMed
98.
Zurück zum Zitat Zhang ZY, Hong D, Nam SH, Kim JM, Paik YH, Joh JW, et al. SIRT1 regulates oncogenesis via a mutant p53-dependent pathway in hepatocellular carcinoma. J Hepatol. 2015;62:121–30.PubMed Zhang ZY, Hong D, Nam SH, Kim JM, Paik YH, Joh JW, et al. SIRT1 regulates oncogenesis via a mutant p53-dependent pathway in hepatocellular carcinoma. J Hepatol. 2015;62:121–30.PubMed
99.
Zurück zum Zitat Lee CW, Wong LL, Tse EY, Liu HF, Leong VY, Lee JM, et al. AMPK promotes p53 acetylation via phosphorylation and inactivation of SIRT1 in liver cancer cells. Cancer Res. 2012;72:4394–404.PubMedPubMedCentral Lee CW, Wong LL, Tse EY, Liu HF, Leong VY, Lee JM, et al. AMPK promotes p53 acetylation via phosphorylation and inactivation of SIRT1 in liver cancer cells. Cancer Res. 2012;72:4394–404.PubMedPubMedCentral
100.
Zurück zum Zitat Blackburn EH. Switching and signaling at the telomere. Cell. 2001;106:661–73.PubMed Blackburn EH. Switching and signaling at the telomere. Cell. 2001;106:661–73.PubMed
101.
Zurück zum Zitat Blasco MA. Telomere length, stem cells and aging. Nat Chem Biol. 2007;3:640–9.PubMed Blasco MA. Telomere length, stem cells and aging. Nat Chem Biol. 2007;3:640–9.PubMed
102.
Zurück zum Zitat de Lange T. Shelterin: the protein complex that shapes and safeguards human telomeres. Genes Dev. 2005;19:2100–10.PubMed de Lange T. Shelterin: the protein complex that shapes and safeguards human telomeres. Genes Dev. 2005;19:2100–10.PubMed
103.
Zurück zum Zitat Palm W, de Lange T. How shelterin protects mammalian telomeres. Annu Rev Genet. 2008;42:301–34.PubMed Palm W, de Lange T. How shelterin protects mammalian telomeres. Annu Rev Genet. 2008;42:301–34.PubMed
104.
Zurück zum Zitat Deng Y, Chan SS, Chang S. Telomere dysfunction and tumour suppression: the senescence connection. Nat Rev Cancer. 2008;8:450–8.PubMedPubMedCentral Deng Y, Chan SS, Chang S. Telomere dysfunction and tumour suppression: the senescence connection. Nat Rev Cancer. 2008;8:450–8.PubMedPubMedCentral
105.
Zurück zum Zitat Oh BK, Jo Chae K, Park C, Kim K, Jung Lee W, Han KH, et al. Telomere shortening and telomerase reactivation in dysplastic nodules of human hepatocarcinogenesis. J Hepatol. 2003;39:786–92.PubMed Oh BK, Jo Chae K, Park C, Kim K, Jung Lee W, Han KH, et al. Telomere shortening and telomerase reactivation in dysplastic nodules of human hepatocarcinogenesis. J Hepatol. 2003;39:786–92.PubMed
106.
Zurück zum Zitat Oh BK, Kim H, Park YN, Yoo JE, Choi J, Kim KS, et al. High telomerase activity and long telomeres in advanced hepatocellular carcinomas with poor prognosis. Lab Invest; J Tech Methods Pathol. 2008;88:144–52. Oh BK, Kim H, Park YN, Yoo JE, Choi J, Kim KS, et al. High telomerase activity and long telomeres in advanced hepatocellular carcinomas with poor prognosis. Lab Invest; J Tech Methods Pathol. 2008;88:144–52.
107.
Zurück zum Zitat Zhang B, Chen J, Cheng AS, Ko BC. Depletion of sirtuin 1 (SIRT1) leads to epigenetic modifications of telomerase (TERT) gene in hepatocellular carcinoma cells. PLoS One. 2014;9, e84931.PubMedPubMedCentral Zhang B, Chen J, Cheng AS, Ko BC. Depletion of sirtuin 1 (SIRT1) leads to epigenetic modifications of telomerase (TERT) gene in hepatocellular carcinoma cells. PLoS One. 2014;9, e84931.PubMedPubMedCentral
108.
Zurück zum Zitat Huang J, Wu S, Barrera J, Matthews K, Pan D. The Hippo signaling pathway coordinately regulates cell proliferation and apoptosis by inactivating Yorkie, the drosophila homolog of YAP. Cell. 2005;122:421–34.PubMed Huang J, Wu S, Barrera J, Matthews K, Pan D. The Hippo signaling pathway coordinately regulates cell proliferation and apoptosis by inactivating Yorkie, the drosophila homolog of YAP. Cell. 2005;122:421–34.PubMed
110.
Zurück zum Zitat Anakk S, Bhosale M, Schmidt VA, Johnson RL, Finegold MJ, Moore DD. Bile acids activate YAP to promote liver carcinogenesis. Cell Rep. 2013;5:1060–9.PubMedPubMedCentral Anakk S, Bhosale M, Schmidt VA, Johnson RL, Finegold MJ, Moore DD. Bile acids activate YAP to promote liver carcinogenesis. Cell Rep. 2013;5:1060–9.PubMedPubMedCentral
111.
Zurück zum Zitat Tao J, Calvisi DF, Ranganathan S, Cigliano A, Zhou L, Singh S, et al. Activation of β-catenin and Yap1 in human hepatoblastoma and induction of hepatocarcinogenesis in mice. Gastroenterology. 2014;147:690–701.PubMedPubMedCentral Tao J, Calvisi DF, Ranganathan S, Cigliano A, Zhou L, Singh S, et al. Activation of β-catenin and Yap1 in human hepatoblastoma and induction of hepatocarcinogenesis in mice. Gastroenterology. 2014;147:690–701.PubMedPubMedCentral
112.
Zurück zum Zitat Sylvester KG, Colnot S. Hippo/YAP, beta-catenin, and the cancer cell: a “menage a trois” in hepatoblastoma. Gastroenterology. 2014;147:562–5.PubMed Sylvester KG, Colnot S. Hippo/YAP, beta-catenin, and the cancer cell: a “menage a trois” in hepatoblastoma. Gastroenterology. 2014;147:562–5.PubMed
113.
Zurück zum Zitat Perra A, Kowalik MA, Ghiso E, Ledda-Columbano GM, Di Tommaso L, Angioni MM, et al. YAP activation is an early event and a potential therapeutic target in liver cancer development. J Hepatol. 2014;61:1088–96.PubMed Perra A, Kowalik MA, Ghiso E, Ledda-Columbano GM, Di Tommaso L, Angioni MM, et al. YAP activation is an early event and a potential therapeutic target in liver cancer development. J Hepatol. 2014;61:1088–96.PubMed
114.
Zurück zum Zitat Mao B, Hu F, Cheng J, Wang P, Xu M, Yuan F, et al. SIRT1 regulates YAP2-mediated cell proliferation and chemoresistance in hepatocellular carcinoma. Oncogene. 2014;33:1468–74.PubMed Mao B, Hu F, Cheng J, Wang P, Xu M, Yuan F, et al. SIRT1 regulates YAP2-mediated cell proliferation and chemoresistance in hepatocellular carcinoma. Oncogene. 2014;33:1468–74.PubMed
115.
Zurück zum Zitat Psyrri A, Arkadopoulos N, Vassilakopoulou M, Smyrniotis V, Dimitriadis G. Pathways and targets in hepatocellular carcinoma. Expert Rev Anticancer Ther. 2012;12:1347–57.PubMed Psyrri A, Arkadopoulos N, Vassilakopoulou M, Smyrniotis V, Dimitriadis G. Pathways and targets in hepatocellular carcinoma. Expert Rev Anticancer Ther. 2012;12:1347–57.PubMed
116.
Zurück zum Zitat Wysocki PJ. Targeted therapy of hepatocellular cancer. Expert Opin Invest Drugs. 2010;19:265–74. Wysocki PJ. Targeted therapy of hepatocellular cancer. Expert Opin Invest Drugs. 2010;19:265–74.
117.
Zurück zum Zitat Menssen A, Hydbring P, Kapelle K, Vervoorts J, Diebold J, Luscher B, et al. The c-MYC oncoprotein, the NAMPT enzyme, the SIRT1-inhibitor DBC1, and the SIRT1 deacetylase form a positive feedback loop. Proc Natl Acad Sci U S A. 2012;109:E187–96.PubMed Menssen A, Hydbring P, Kapelle K, Vervoorts J, Diebold J, Luscher B, et al. The c-MYC oncoprotein, the NAMPT enzyme, the SIRT1-inhibitor DBC1, and the SIRT1 deacetylase form a positive feedback loop. Proc Natl Acad Sci U S A. 2012;109:E187–96.PubMed
118.
Zurück zum Zitat Mao B, Zhao G, Lv X, Chen HZ, Xue Z, Yang B, et al. Sirt1 deacetylates c-Myc and promotes c-Myc/Max association. Int J Biochem Cell Biol. 2011;43:1573–81.PubMed Mao B, Zhao G, Lv X, Chen HZ, Xue Z, Yang B, et al. Sirt1 deacetylates c-Myc and promotes c-Myc/Max association. Int J Biochem Cell Biol. 2011;43:1573–81.PubMed
119.
Zurück zum Zitat Jang KY, Noh SJ, Lehwald N, Tao GZ, Bellovin DI, Park HS, et al. SIRT1 and c-Myc promote liver tumor cell survival and predict poor survival of human hepatocellular carcinomas. PLoS One. 2012;7, e45119.PubMedPubMedCentral Jang KY, Noh SJ, Lehwald N, Tao GZ, Bellovin DI, Park HS, et al. SIRT1 and c-Myc promote liver tumor cell survival and predict poor survival of human hepatocellular carcinomas. PLoS One. 2012;7, e45119.PubMedPubMedCentral
120.
Zurück zum Zitat Cheng HL, Mostoslavsky R, Saito S, Manis JP, Gu Y, Patel P, et al. Developmental defects and p53 hyperacetylation in Sir2 homolog (SIRT1)-deficient mice. Proc Natl Acad Sci U S A. 2003;100:10794–9.PubMedPubMedCentral Cheng HL, Mostoslavsky R, Saito S, Manis JP, Gu Y, Patel P, et al. Developmental defects and p53 hyperacetylation in Sir2 homolog (SIRT1)-deficient mice. Proc Natl Acad Sci U S A. 2003;100:10794–9.PubMedPubMedCentral
121.
Zurück zum Zitat Wang RH, Sengupta K, Li C, Kim HS, Cao L, Xiao C, et al. Impaired DNA damage response, genome instability, and tumorigenesis in SIRT1 mutant mice. Cancer Cell. 2008;14:312–23.PubMedPubMedCentral Wang RH, Sengupta K, Li C, Kim HS, Cao L, Xiao C, et al. Impaired DNA damage response, genome instability, and tumorigenesis in SIRT1 mutant mice. Cancer Cell. 2008;14:312–23.PubMedPubMedCentral
122.
Zurück zum Zitat Ip BC, Hu KQ, Liu C, Smith DE, Obin MS, Ausman LM, et al. Lycopene metabolite, apo-10′-lycopenoic acid, inhibits diethylnitrosamine-initiated, high fat diet-promoted hepatic inflammation and tumorigenesis in mice. Cancer Prev Res. 2013;6:1304–16. Ip BC, Hu KQ, Liu C, Smith DE, Obin MS, Ausman LM, et al. Lycopene metabolite, apo-10′-lycopenoic acid, inhibits diethylnitrosamine-initiated, high fat diet-promoted hepatic inflammation and tumorigenesis in mice. Cancer Prev Res. 2013;6:1304–16.
123.
Zurück zum Zitat Tai DI, Tsai SL, Chang YH, Huang SN, Chen TC, Chang KS, et al. Constitutive activation of nuclear factor kappaB in hepatocellular carcinoma. Cancer. 2000;89:2274–81.PubMed Tai DI, Tsai SL, Chang YH, Huang SN, Chen TC, Chang KS, et al. Constitutive activation of nuclear factor kappaB in hepatocellular carcinoma. Cancer. 2000;89:2274–81.PubMed
124.
Zurück zum Zitat Gang D, Hongwei H, Hedai L, Ming Z, Qian H, Zhijun L. The tumor suppressor protein menin inhibits NF-κB-mediated transactivation through recruitment of Sirt1 in hepatocellular carcinoma. Mol Biol Rep. 2013;40:2461–6.PubMed Gang D, Hongwei H, Hedai L, Ming Z, Qian H, Zhijun L. The tumor suppressor protein menin inhibits NF-κB-mediated transactivation through recruitment of Sirt1 in hepatocellular carcinoma. Mol Biol Rep. 2013;40:2461–6.PubMed
125.
Zurück zum Zitat Tanno M, Sakamoto J, Miura T, Shimamoto K, Horio Y. Nucleocytoplasmic shuttling of the NAD+-dependent histone deacetylase SIRT1. J Biol Chem. 2007;282:6823–32.PubMed Tanno M, Sakamoto J, Miura T, Shimamoto K, Horio Y. Nucleocytoplasmic shuttling of the NAD+-dependent histone deacetylase SIRT1. J Biol Chem. 2007;282:6823–32.PubMed
126.
Zurück zum Zitat Jin Q, Yan T, Ge X, Sun C, Shi X, Zhai Q. Cytoplasm-localized SIRT1 enhances apoptosis. J Cell Physiol. 2007;213:88–97.PubMed Jin Q, Yan T, Ge X, Sun C, Shi X, Zhai Q. Cytoplasm-localized SIRT1 enhances apoptosis. J Cell Physiol. 2007;213:88–97.PubMed
127.
Zurück zum Zitat Song S, Luo M, Song Y, Liu T, Zhang H, Xie Z. Prognostic role of SIRT1 in hepatocellular carcinoma. J Coll Physicians Surg Pak: JCPSP. 2014;24:849–54.PubMed Song S, Luo M, Song Y, Liu T, Zhang H, Xie Z. Prognostic role of SIRT1 in hepatocellular carcinoma. J Coll Physicians Surg Pak: JCPSP. 2014;24:849–54.PubMed
Metadaten
Titel
Emerging role of silent information regulator 1 (SIRT1) in hepatocellular carcinoma: a potential therapeutic target
verfasst von
Yuting Wu
Xiaoming Meng
Cheng Huang
Jun Li
Publikationsdatum
01.06.2015
Verlag
Springer Netherlands
Erschienen in
Tumor Biology / Ausgabe 6/2015
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-3488-x

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CUP-Syndrom: Künstliche Intelligenz kann Primärtumor finden

30.04.2024 Künstliche Intelligenz Nachrichten

Krebserkrankungen unbekannten Ursprungs (CUP) sind eine diagnostische Herausforderung. KI-Systeme können Pathologen dabei unterstützen, zytologische Bilder zu interpretieren, um den Primärtumor zu lokalisieren.

Sind Frauen die fähigeren Ärzte?

30.04.2024 Gendermedizin Nachrichten

Patienten, die von Ärztinnen behandelt werden, dürfen offenbar auf bessere Therapieergebnisse hoffen als Patienten von Ärzten. Besonders gilt das offenbar für weibliche Kranke, wie eine Studie zeigt.

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.

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