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ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Issue 6
Jun.  2015
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Article Contents

PI3K / Akt / mTOR signaling pathway and malignant hepatobiliary tumors

DOI: 10.3969/j.issn.1001-5256.2015.06.040
  • Published Date: 2015-06-20
  • Phosphoinositide- 3 kinase / protein kinase- B / mammalian target of rapamycin( PI3 K / Akt / m TOR) signaling pathway is involved in many important biological processes such as cell metabolism,growth,proliferation,and angiogenesis. And its high- level activation is closely related to the development and progression of many malignant tumors. In this paper,m TOR and PI3 K / Akt / m TOR signaling pathway are introduced,and their action mechanisms in the development and progression of hepatocellular carcinoma,cholangiocellular carcinoma,cholangiocarcinoma,and gallbladder carcinoma are expounded,and then the role of m TOR inhibitors in the treatment of malignant hepatobiliary tumors is briefly described. It is thought that the PI3 K / Akt / m TOR signaling pathway provides new therapeutic targets for malignant hepatobiliary tumors in advanced stage and the constant development of new m TOR inhibitors provides some new hope for the patients with malignant hepatobiliary tumors in advanced stage.

     

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  • [1] JEMAL A,BRAY F,CENTER MM,et al.Global cancer statistics[J].CA Cancer J Clin,2011,61(2):69-90.
    [2]FLORES A,MARRERO JA.Emerging trends in hepatocellular carcinoma:focus on diagnosis and therapeutics[J].Clin Med Insights Oncol,2014,8:71-76.
    [3]ROA I,IBACACHE G,MUNOZ S,et al.Gallbladder cancer in Chile:Pathologic characteristics of survival and prognostic factors:analysis of 1,366 cases[J].Am J Clin Pathol,2014,141(5):675-682.
    [4]MEMMOTT RM,DENNIS PA.Akt-dependent and-independent mechanisms of m TOR regulation in cancer[J].Cell Signal,2009,21(5):656-664.
    [5]HWANG SK,KIM HH.The functions of m TOR in ischemic diseases[J].BMB Rep,2011,44(8):506-511.
    [6]MARTINEZ-LOPEZ N,VARELA-REY M,FERNANDEZRAMOS D,et al.Activation of LKB1-Akt pathway independent of phosphoinositide 3-kinase plays a critical role in the proliferation of hepatocellular carcinoma from nonalcoholic steatohepatitis[J].Hepatology,2010,52(5):1621-1631.
    [7]WATANABE S,HORIE Y,SUZUKI A.Hepatocyte-specific Pten-deficient mice as a novel model for nonalcoholic steatohepatitis and hepatocellular carcinoma[J].Hepatol Res,2005,33(2):161-166.
    [8]CALVISI DF,WANG C,HO C,et al.Increased lipogenesis,induced by AKT-m TORC1-RPS6 signaling,promotes development of human hepatocellular carcinoma[J].Gastroenterology,2011,140(3):1071-1083.
    [9]MENON S,YECIES JL,ZHANG HH,et al.Chronic activation of m TOR complex 1 is sufficient to cause hepatocellular carcinoma in mice[J].Sci Signal,2012,5(217):ra24.
    [10]SAHIN F,KANNANGAI R,ADEGBOLA O,et al.m TOR and P70S6 kinase expression in primary liver neoplasms[J].Clin Cancer Res,2004,10(24):8421-8425.
    [11]VILLANUEVA A,CHIANG DY,NEWELL P,et al.Pivotal role of m TOR signaling in hepatocellular carcinoma[J].Gastroenterology,2008,135(6):1972-1983.
    [12]NAKANISHI K,SAKAMOTO M,YAMASAKI S,et al.Akt phosphorylation is a risk factor for early disease recurrence and poor prognosis in hepatocellular carcinoma[J].Cancer,2005,103(2):307-312.
    [13]ZHOU L,HUANG Y,LI J,et al.The m TOR pathway is associated with the poor prognosis of human hepatocellular carcinoma[J].Med Oncol,2010,27(2):255-261.
    [14]MCKAY SC,UNGER K,PERICLEOUS S,et al.Array comparative genomic hybridization identifies novel potential therapeutic targets in cholangiocarcinoma[J].HPB(Oxford),2011,13(5):309-319.
    [15]LEE D,DO IG,CHOI K,et al.The expression of phospho-AKT1and phospho-MTOR is associated with a favorable prognosis independent of PTEN expression in intrahepatic cholangiocarcinomas[J].Mod Pathol,2012,25(1):131-139.
    [16]WANG Z,ZHENG T,WU Q,et al.Immunohistochemical analysis of the m TOR pathway in intrahepatic cholangiocarcinoma[J].Neoplasma,2012,59(2):137-141.
    [17]CHUNG JY,HONG SM,CHOI BY,et al.The expression of phospho-AKT,phospho-m TOR,and PTEN in extrahepatic cholangiocarcinoma[J].Clin Cancer Res,2009,15(2):660-667.
    [18]HERBERGER B,PUHALLA H,LEHNERT M,et al.Activated mammalian target of rapamycin is an adverse prognostic factor in patients with biliary tract adenocarcinoma[J].Clin Cancer Res,2007,13(16):4795-4799.
    [19]LEAL P,GARCIA P,SANDOVAL A,et al.AKT/m TOR substrate P70S6K is frequently phosphorylated in gallbladder cancer tissue and cell lines[J].Onco Targets Ther,2013,6:1373-1384.
    [20]LEAL P,GARCIA P,SANDOVAL A,et al.Immunohistochemical expression of phospho-m TOR is associated with poor prognosis in patients with gallbladder adenocarcinoma[J].Arch Pathol Lab Med,2013,137(4):552-557.
    [21]ZHU AX,ABRAMS TA,MIKSAD R,et al.Phase 1/2 study of everolimus in advanced hepatocellular carcinoma[J].Cancer,2011,117(22):5094-5102.
    [22]MASUDA M,SHIMOMURA M,KOBAYASHI K,et al.Growth inhibition by NVP-BEZ235,a dual PI3K/m TOR inhibitor,in hepatocellular carcinoma cell lines[J].Oncol Rep,2011,26(5):1273-1279.
    [23]THOMAS HE,MERCER CA,CARNEVALLI LS,et al.m TOR inhibitors synergize on regression,reversal of gene expression,and autophagy in hepatocellular carcinoma[J].Sci Transl Med,2012,4(139):139r-184r.
    [24]TAM KH,YANG ZF,LAU CK,et al.Inhibition of m TOR enhances chemosensitivity in hepatocellular carcinoma[J].Cancer Lett,2009,273(2):201-209.
    [25]OKADA T,SAWADA T,KUBOTA K.Rapamycin inhibits growth of cholangiocarcinoma cells[J].Hepatogastroenterology,2009,56(89):6-10.
    [26]RIZELL M,ANDERSSON M,CAHLIN C,et al.Effects of the m TOR inhibitor sirolimus in patients with hepatocellular and cholangiocellular cancer[J].Int J Clin Oncol,2008,13(1):66-70.
    [27]ZONG H,YIN B,ZHOU H,et al.Inhibition of m TOR pathway attenuates migration and invasion of gallbladder cancer via EMT inhibition[J].Mol Biol Rep,2014,41(7):4507-4512.
    [28]WU Q,KIGUCHI K,KAWAMOTO T,et al.Therapeutic effect of rapamycin on gallbladder cancer in a transgenic mouse model[J].Cancer Res,2007,67(8):3794-3800.
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