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自噬是维持细胞存活、分化、生长和稳态所必须的一种溶酶体降解途径(Levine and Kroemer,2008)。最近的大量研究证实自噬与多种肿瘤细胞的恶性转化和肿瘤细胞的生长有关。哺乳动物雷帕霉素靶蛋白(m TOR)和自噬相关基因Beclin1与细胞自噬关系密切,其可通过调节细胞自噬活性而在肿瘤的发生发展过程中发挥重要的作用。目前,有关肿瘤细胞自噬性死亡的研究受到越来越多人的关注,它很可能成为肿瘤治疗的新靶点。因此,深入研究m TOR、Beclin1在调控自噬过程中与肿瘤的发生发展关系可能对临床上有关肿瘤治疗方面的研究有重要意义。本文现就对自噬通路中m TOR、Beclin1与肿瘤关系的研究进展作一简要概述。
Abstract:Autophagy is a lysosomal degradation pathway that is essential for cellular survival, differentiation,development and homeostasis(Levine and Kroemer, 2008). Recent studies have demonstrated that autophagy is related to the malignant transformation and growth of cancer cells. Mammalian target of rapamycin(m TOR) and the autophagy related gene Beclin1 have close relationship with autophagy, which can play an important role through regulating the autophagic activity in the genesis and progression of tumor cells. At present, researches about the autophagic death of tumor cells are concerned by more and more people. It is likely to be a new target for tumorous therapy. Therefore, the in-depth researches on the relationship between m TOR, Beclin1 during the process of regulating autophagic activity and tumorous genesis, progression may have important significance for the clinical treatment of tumor. Now, the latest progress of the relationship between m TOR, Beclin1 and tumor in autophagy pathway is briefly summarized.
Amaravadi R.K.,Lippincott-Schwartz J.,Yin X.M.,Weiss W.A.,Takebe N.,Timmer W.,DiPaola R.S.,Lotze M.T.,and White E.,2011,Principles and current strategies for targeting autophagy for cancer treatment,Clinical Cancer Research,17(4):654-666
Bar-Peled L.,Chantranupong L.,Cherniack A.D.,Chen W.W.,Ottina K.A.,Grabiner B.C.,Spear E.D.,Carter S.L.,Meyerson M.,and Sabatini D.M.,2013,A tumor suppressor complex with GAP activity for the rag GTPases that signal amino acid sufficiency to mTORC1,Science,340(6136):1100-1106
Chen N.,and Karantza-Wadsworth V.,2009,Role and regulation of autophagy in cancer,Biochimica et Biophysica Acta,1793(9):1516-1523
Doherty E.,Oaks Z.,and Perl A.,2014,Increased mitochondrial electron transport chain activity at complex I is regulated by N-acetylcysteine in lymphocytes of patients with systemic lupus erythematosus,Antiox.Redox Signal.,21(1):56-65
Dong M.,Wan X.B.,Yuan Z.Y.,Wei L.,Fan X.J.,Wang T.T.,Lv Y.C.,Li X,Chen Z.H,Chen J,Lin Q,Wen J.Y,Ma X.K.,Liu Q.,and Wu X.Y.,2013,Low expression of Beclin 1 and elevated expression of HIF-lαrefine distant metastasis risk and predict poor prognosis of ER-positive,HER2-negative breast cancer,Medical Oncology,30(1):355
Dorr J.R.,Yu Y.,Milanovic M.,Beuster G.,Zasada C,D(a|")britz J.H.,Lisec J.,Lenze D.,Gerhardt A.,Schleicher K.,Kratzat S.,Purf(u|")rst B.,Walenta S.,Mueller-Klieser W.,Graler M.,Hummel M.,Keller U.,Buck A.K.,Darken B.,Willmitzer L.,Reimann M.,Kempa S.,Lee S.,and Schmitt C.A.,2013,Synthetic lethal metabolic targeting of cellular senescence in cancer therapy,Nature,501(7467):421-425
Fonseca B.D.,Diering G.H.,Bidinosti M.A.,Dalai K.,Alain T.,Balgi A.D.,Forestieri R.,Nodwell M.,Rajadurai C.V.,Gunaratnam C,Tee A.R.,Duong F.,Andersen R.J.,Orlowski J.,Numata M.,Sonenberg N.,and Roberge M.,2012,Structure-activity analysis of niclosamide reveals potential role for cytoplasmic pH in control of mammalian target of ra pamycin complex 1(mTORCl)signaling,J.Biol.Chem,287(21):17530-17545
Galluzzi L.,Pietrocola F.,Bravo-San Pedro J.M.,Amaravadi R.K.,Baehrecke E.H.,Cecconi F.,Codogno P.,Debnath J.,Gewirtz D.A.,Karantza V.,Kimmelman A.,Kumar S.,Levine B.,Maiuri M.C.,Martin S.J.,Penninger J.,Piacentini M.,Rubinsztein D.C.,Simon H.U.,Simonsen A.,Thorburn A.M.,Velasco G.,Ryan K.M.,and Kroemer G.,2015,Autophagy in malignant transformation and cancer progression,The EMBO Journal,34(7):856-880
Guertin D.A.,Stevens D.M.,Saitoh M.,Kinkel S.,Crosby K.,Sheen J.H.,Mullholland D.J.,Magnuson M.A.,Wu H.,and Sabatini D.M.,2009,The mTOR complex 2 is required for the development of prostate cancer induced by Pten loss in mice,Cancer Cell,15(2):148-159
Guo J.Y.,Xia B.,and White E.,2013,Autophagy-mediated tumor promotion,Cell,155(6):1216-1219
Han Y.,Xue X.F.,Shen H.G.,Guo X.B.,Wang X,Yuan B,Guo X.P.,Kuang Y.T.,Zhi Q.M.,and Zhao H.,2014,Prognostic significance of Beclin-1 expression in colorectal cancer:a meta-analysis,Asian Pac.J.Cancer Prev.,15(11):4583-4587
Huo Y.,Cai H.,Teplova I.,Bowman-Colin C,Chen G.,Price S.,Barnard N.,Ganesan S.,Karantza V.,White E.,and Xia B.,2013,Autophagy opposes p53-mediated tumor barrier to facilitate tumorigenesis in a model of PALB2-associated hereditary breast cancer,Cancer Discovery,3(8):894-907
Kang R.,Zeh H.J.,Lotze M.T.,and Tang D.,2011,The Beclin 1network regulates autophagy and apoptosis,Cell Death&Differentiation,18(4):571-580
Klionsky D.J.,Cuervo A.M.,and Seglen P.O.,2007,Methods for monitoring autophagy from yeast to human,Autophagy,3(3):181-206
Laddha S.V.,Ganesan S.,Chan C.S.,and White E.,2014,Mutational landscape of the essential autophagy gene BECN1 in human cancers,Molecular Cancer Research,12(4):485-490
Lamming D.W.,Ye L.,Katajisto P.,Goncalves M.D.,Saitoh M.,Stevens D.M.,Davis J.G.,Salmon A.B.,Richardson A.,Ahima R.S.,Guertin D.A.,Sabatini D.M.,and Baur J.A.,2012,Rapamycin-induced insulin resistance is mediated by mT0RC2 loss and uncoupled from longevity,Science,335(6076):1638-1643
Laplante M.,and Sabatini D.M.,2013,Regulation of mTORCl and its impact on gene expression at a glance,Journal of Cell Science,126(8):1713-1719
Lawrence M.S.,Stojanov P.,Mermel C.H.,Robinson J.T.,Garraway L.A.,Golub T.R.,Meyerson M.,Gabriel S.B.,Lander E.S.,and Getz G.,2014,Discovery and saturation analysis of cancer genes across 21 tumour types,Nature,505(7484):495-501
Levine B.,and Kroemer G.,2008,Autophagy in the pathogenesis of disease,Cell,132(1):27-42
Li C,Lee P.S.,Sun Y.,Gu X.,Zhang E.,Guo Y.,Wu C.L.,Auricchio N.,Priolo C,Li J.,Csibi A.,Parkhitko A.,Morrison T.,Planaguma A.,Kazani S.,Israel E.,Xu K.F.,Henske E.P.,Blenis J.,Levy B.D.,Kwiatkowski D.,and Yu J.J.,2014,Estradiol and mT0RC2 cooperate to enhance prostaglandin biosynthesis an d tumorigenesis in TSC2-deficient LAM cells,J.Exp.Med.,211(1):15-28
Liu B.,Yang L.,Huang B.,Cheng M,Wang H.,Li Y.,Huang D.,Zheng J.,Li Q.,Zhang X.,Ji W.,Zhou Y.,and Lu J.,2012,A Functional copy-number variation in MAPKAPK2 predicts risk and prognosis of lung cancer,American Journal of Human Genetics,91(2):384-390
Liu G.,Bi Y.,Shen B.,Yang H.,Zhang Y.,Wang X.,Liu H.,Lu Y.,Liao J.,Chen X.,and Chu Y.,2014,SIRT1 limits the function and fate of myeloid-derived suppressor cells in tumors by orchestrating HIF-1α-dependent glycolysis,Cancer Res.,74(3):727-737
Liu P.,Gan W.,Inuzuka H.,Lazorchak A.S.,Gao D.,Arojo O.,Liu D.,Wan L.,Zhai B.,Yu Y.,Yuan M.,Kim B.M.,Shaik S.,Menon S.,Gygi S.P.,Lee T.H.,Asara J.M.,Manning B.D.,Blenis J.,Su B.,and Wei W.,2013,Sin1 phosphorylation impairs mT0RC2 complex integrity and inhibits downstream Akt signalling to suppress tumorigenesis,Nat.Cell Biol,15(11):1340-1350
Lock R.,Kenific C.M.,Leidal A.M.,Salas E.,and Debnath J.,2014,Autophagy-dependent production of secreted factors facilitates oncogenic RAS-driven invasion,Cancer Discovery,4(4):466-479
Ma X.H.,Piao S.F.,Dey S.,McAfee Q.,Karakousis G.,Villanueva J.,Hart L.S.,Levi S.,Hu J.,Zhang G.,Lazova R.,Klump V.,Pawelek J.M.,Xu X.,Xu W.,Schuchter L.M.,Davies M.A.,Herlyn M.,Winkler J.,Koumenis C,and Amaravadi R.K.,2014,Targeting ER stress-induced autophagy overcomes BRAF inhibitor resistance in melanoma,The Journal of Clinical Investigation,124(3):1406-1417
Marsh T.,and Debnath J.,2015,Ironing out VPS34 inhibition,Nature Cell Biology,17(1):1-3
Mihaylova M.M.,and Shaw R.J.,2011,The AMPK signalling pathway coordinates cell growth,autophagy and metabolism,Nature Cell Biology,13(9):1016-1023
Mizushima N.,Yoshimori T.,and Ohsumi Y.,2011,The role oi Atg proteins in autophagosome formation,Annu.Rev.Cell Dev.Biol.,27:107-132
Noda T.,and Ohsumi Y.,1998,Tor,a phosphatidylinositol kinase homologue,controls autophagy in yeast,Journal of Biological Chemistry,273(7):3963-3966
Qi W.X.,Huang Y.J.,Yao Y.,Shen Z.,and Min D.L.,2013,Incidence and risk of treatment-related mortality with mTOR inhibitors everolimus and temsirolimus in cancer patients:a meta-analysis,PLoS ONE,8(6):e65166
Rohatgi R.A.,Janusis J.,Leonard D.,Bellve K.D.,Fogarty K.E.,Baehrecke E.H.,Corvera S.,and Shaw L.M.,2015,Beclin 1regulates growth factor receptor signaling in breast cancer,Oncogene,Epub ahead of print
Rosenfeldt M.T.,O'Prey J.,Morton J.P.,Nixon C,MacKay G.,Mrowinska A.,Au A.,Rai T.S.,Zheng L.,Ridgway R.,Adams P.D.,Anderson K.I.,Gottlieb E.,Sansom O.J.,and Ryan K.M.,2013,p53 status determines the role of autophagy in pancreatic tumour development,Nature,504(7479):296-300
Roy S.,and Debnath J.,2010,Autophagy and tumorigenesis,Semin Immunopathol,32(4):383-396
Sahni S.,Merlot A.M.,Krishan S.,Jansson P.J.,and Richardson D.R.,2014,Gene of the month:BECN1,J.Clin.Pathol.,67(8):656-660
Semenza G.L.,2013,HIF-1 mediates metabolic responses to in tratumoral hypoxia and oncogenic mutations,J.Clin.Invest.,123(9):3664-3671
Singletary K.,and Milner J.,2008,Diet,autophngy,and cancer:a review,Cancer Epidemiol Biomarkers Prev.,17(7):1596-1610
Song S.,Chen D.,Lu J.,Liao J.,Luo Y.,Yang Z.,Fu X.,Fan X.,Wei Y,Yang L,Wang L,and Wang J,2011,NFk Bl and NFk BIA polymorphisms are associated with increased risk for sporadic colorectal cancer in a Southern Chinese Population,Plos One,6(6):e21726
Sun Q.,Chen X.,Ma J.,Peng H.,Wang F.,Zha X.,Wang Y.,Jing Y.,Yang H.,Chen R.,Chang L.,Zhang Y.,Goto J.,Onda H.,Chen T,Wang M.R.,Lu Y,You H,Kwiatkowski D.,and Zhang H.,2011,Mammalian target of rapamycin up-regulation of pyruvate kinase isoenzyme type M2 is critical for aerobic glycolysis and tumor growth,Proc.Natl.Acad.Sci.USA,108(10):4129-4134
Sun Y,Liu J.H,Jin L,Sui Y.X,Han L.L,and Huang Y,2015,Effect of autophagy-related beclinl on sensitivity of Cisplatin-resistant ovarian cancer cells to chemotherapeutic agents,Asian Pac.J.Cancer P.,16(7):2785-2791
Sun Y.,Liu J.H.,Jin L.,Sui Y.X.,Lai L.,and Yang Y.,2014,Inhibition of Beclinl expression enhances cisplatin-induced apoptosis through a mitochondrial-dependent pathway in human ovarian cancer SKOV3/DDP cells,Oncology Res.,21(5):261-269
Vogelstein B.,Papadopoulos N.,Velculescu V.E.,Zhou S.,Diaz L.A.Jr.,and Kinzler K.W.,2013,Cancer Genome Landscapes,Science,339(6127):1546-1558
Wang J.,Pan X.L.,Ding L.J.,Liu D.Y.,Da-Peng L.,and Jin T.,2013,Aberrant expression of Beclin-1 and LC3 correlates with poor prognosis of human hypopharyngeal squamous cell carcinoma,PloS One,8(7):e69038
Wang S.M.,Li X.H.,and Xiu Z.L.,2014,Over-expression of Beclin-1 facilitates acquired resistance to histone deacetylase inhibitor-induced apoptosis,Asian Pac.J.Cancer Prev.,15(18):7913-7917
Wei H.,Wei S.,Gan B.,Peng X.,Zou W.,and Guan J.L.,2011,Suppression of autophagy by FIP200 deletion inhibits mammary tumorigenesis,Genes Dev.,25(14):1510-1527
White E.,2015,The role for autophagy in cancer,The Journal of Clinical Investigation,125(1):42-46
Xie X.,White E.P.,and Mehnert J.M.,2013,Coordinate autophagy and mTOR pathway inhibition enhances cell death in melanoma,PloS One,8(1):e55096
Xu B.,Meng Y.,and Jiang Y.D.,2015,Expression and significance of Beclin-1,PTEN,p53 in colorectal cancer,Modern Oncology,23(4):530-534(许斌,孟媛,姜彦多,2015,自噬相关基因BeClin-1与抑癌基因PTEN,p53在大肠癌中的表达和意义,现代肿瘤医学,23(4):530-534)
Yin Y.,Choi S.C.,Xu Z.,Perry D.J.,Seay H.,Croker B.P.,Sobel E.S.,Brusko T.M.,and Morel L.,2015,Normalization of CD4+T cell metabolism reverses lupus,Sci.Transl.Med.,7(274):274ra18
基本信息:
DOI:10.13417/j.gab.034.001656
中图分类号:R730.2
引用信息:
[1]王远航,夏盛源,王芳,等.自噬通路中mTOR、Beclin1与肿瘤关系研究的最新进展[J].基因组学与应用生物学,2015,34(08):1656-1662.DOI:10.13417/j.gab.034.001656.
基金信息:
国家自然科学基金项目(81102159,81302378);; 广州市教育局广州市属高校“羊城学者”科研项目(12A010D);; 广州市教育局广州市属高校科研计划项目(2012C207)共同资助
2015-08-25
2015-08-25