细胞自噬与非小细胞肺癌的研究进展
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摘要
自噬不仅与NSCLC的增殖、侵袭及转移密切相关,而且在抗肿瘤药物介导的细胞死亡中发挥重要作用,因此,研发以自噬为靶点的药物可能是人类疾病治疗应用的新趋势。多种信号通路参与了细胞自噬的调控,明确细胞自噬的调控机制能为NSCLC的靶向治疗提供新思路。
Autophagy is not only closely related to proliferation, invasion and metastasis of NSCLC, but also plays an important role in anti-tumor drug-mediated cell death. Thus, the development of drugs targeting autophagy may be a new trend in the treatment of human diseases. Various signaling pathways have been involved in the regulation of autophagy, and clarifying regulation mechanism of cell autophagy can provide new ideas for targeted therapy of NSCLC.
Autophagy is not only closely related to proliferation, invasion and metastasis of NSCLC, but also plays an important role in anti-tumor drug-mediated cell death. Thus, the development of drugs targeting autophagy may be a new trend in the treatment of human diseases. Various signaling pathways have been involved in the regulation of autophagy, and clarifying regulation mechanism of cell autophagy can provide new ideas for targeted therapy of NSCLC.
引文
[1]Siegel RL,Miller KD,Jemal A.Cancer statistics,2018.CA Cancer J Clin,2018,68:7-30
[2]Zhou C,Yao LD.Strategies to improve outcomes of patients with EGFR-mutant non-small cell lung cancer:review of the literature.J Thorac Oncol,2016,11:174-86
[3]Takeshige K,Baba M,Tsuboi S,et al.Autophagy in yeast demonstrated with proteinase-deficient mutants and conditions for its induction.J Cell Biol,1992,119:301-11
[4]Wen X,Klionsky DJ.An overview of macroautophagy in yeast.J Mol Biol,2016,428:1681-99
[5]Sahu R,Kaushik S,Clement CC,et al.Microautophagy of cytosolic proteins by late endosomes.Dev Cell,2011,20:131-9
[6]Patel AS,Morse D,Choi AM.Regulation and functional significance of autophagy in respiratory cell biology and disease.Am J Respir Cell Mol Biol,2013,48:1-9
[7]Wong PM,Puente C,Ganley IG,et al.The ULK1complex:sensing nutrient signals for autophagy activation.Autophagy,2013,9:124-37
[8]Puente C,Hendrickson RC,Jiang X.Nutrient-regulated phosphorylation of ATG13 inhibits starvation-induced autophagy.J Biol Chem,2016,291:6026-35
[9]Saleiro D,Mehrotra S,Kroczynska B,et al.Central role of ULK1 in type I interferon signaling.Cell Rep,2015,11:605-17
[10]Shimobayashi M,Hall MN.Making new contacts:the mTOR network in metabolism and signalling crosstalk.Nat Rev Mol Cell Biol,2014,15:155-62
[11]Egan DF,Chun MG,Vamos M,et al.Small molecule inhibition of the autophagy kinase ULK1 and identification of ULK1 substrates.Mol Cell,2015,59:285-97
[12]Park JM,Jung CH,Seo M,et al.The ULK1 complex mediates MTORC1 signaling to the autophagy initiation machinery via binding and phosphorylating ATG14.Autophagy,2016,12:547-64
[13]Hardie DG.AMPK--sensing energy while talking to other signaling pathways.Cell Metab,2014,20:939-52
[14]Hoyer-Hansen M,Bastholm L,Szyniarowski P,et al.Control of macroautophagy by calcium,calmodulindependent kinase kinase-β,and Bcl-2.Mol Cell,2007,25:193-205
[15]Wei Y,Zou Z,Becker N,et al.EGFR-mediated Beclin 1phosphorylation in autophagy suppression,tumor progression,and tumor chemoresistance.Cell,2013,154:1269-84
[16]Nazio F,Strappazzon F,Antonioli M,et al.mTOR inhibits autophagy by controlling ULK1 ubiquitylation,selfassociation and function through AMBRA1 and TRAF6.Nat Cell Biol,2013,15:406-16
[17]Liang XH,Jackson S,Seaman M,et al.Induction of autophagy and inhibition of tumorigenesis by beclin 1.Nature,1999,402:672-6
[18]Yue Z,Jin S,Yang C,et al.Beclin 1,an autophagy gene essential for early embryonic development,is a haploinsufficient tumor suppressor.Proc Natl Acad Sci USA,2003,100:15077-82
[19]White E.The role for autophagy in cancer.J Clin Invest,2015,125:42-6
[20]Mathew R,White E.Autophagy in tumorigenesis and energy metabolism:friend by day,foe by night.Curr Opin Genet Dev,2011,21:113-9
[21]Mathew R,Karp CM,Beaudoin B,et al.Autophagy suppresses tumorigenesis through elimination of p62.Cell,2009,137:1062-75
[22]Kenific CM,Thorburn A,Debnath J.Autophagy and metastasis:another double-edged sword.Curr Opin Cell Biol,2010,22:241-5
[23]Sosa MS,Bragado P,Debnath J,et al.Regulation of tumor cell dormancy by tissue microenvironments and autophagy.Adv Exp Med Biol,2013,734:73-89
[24]Guo JY,Chen HY,Mathew R,et al.Activated Ras requires autophagy to maintain oxidative metabolism and tumorigenesis.Genes Dev,2011,25:460-70
[25]Liu G,Pei F,Yang F,et al.Role of autophagy and apoptosis in non-small-cell lung cancer.Int J Mol Sci,2017,18:367
[26]Guo JY,Karsli-Uzunbas G,Mathew R,et al.Autophagy suppresses progression of K-ras-induced lung tumors to oncocytomas and maintains lipid homeostasis.Genes Dev,2013,27:1447-61
[27]Strohecker AM,Guo JY,Karsli-Uzunbas G,et al.Autophagy sustains mitochondrial glutamine metabolism and growth of BrafV600E-driven lung tumors.Cancer Discov,2013,3:1272-85
[28]Zhou Y,Huang N,Wu J,et al.Silencing of NRAGEinduces autophagy via AMPK/Ulk1/Atg13 signaling pathway in NSCLC cells.Tumour Biol,2017,39:1010428317709676
[29]Rothschild SI,Gautschi O,Batliner J,et al.MicroRNA-106a targets autophagy and enhances sensitivity of lung cancer cells to Src inhibitors.Lung Cancer,2017,107:73-83
[30]Cai J,Li R,Xu X,et al.CK1αsuppresses lung tumour growth by stabilizing PTEN and inducing autophagy.Nat Cell Biol,2018,20:465-78
[31]Ramirez M,Rajaram S,Steininger RJ,et al.Diverse drugresistance mechanisms can emerge from drug-tolerant cancer persister cells.Nat Commun,2016,7:10690
[32]Liang C,Zhang X,Wang HM,et al.MicroRNA-18a-5p functions as an oncogene by directly targeting IRF2 in lung cancer.Cell Death Dis,2017,8:e2764
[33]Ye Z,Fang B,Pan J,et al.miR-138 suppresses the proliferation,metastasis and autophagy of non-small cell lung cancer by targeting Sirt1.Oncol Rep,2017,37:3244-52
[34]Mi S,Xiang G,Yuwen D,et al.Inhibition of autophagy by andrographolide resensitizes cisplatin-resistant non-small cell lung carcinoma cells via activation of the Akt/mTORpathway.Toxicol Appl Pharmacol,2016,310:78-86
[35]Yuwen DL,Sheng BB,Liu J,et al.MiR-146a-5p level in serum exosomes predicts therapeutic effect of cisplatin in non-small cell lung cancer.Eur Rev Med Pharmacol Sci,2017,21:2650-8
[36]Zarogoulidis P,Petanidis S,Domvri K,et al.Autophagy inhibition upregulates CD4+tumor infiltrating lymphocyte expression via miR-155 regulation and TRAIL activation.Mol Oncol,2016,10:1516-31
[37]Chen X,Wang P,Guo F,et al.Autophagy enhanced the radioresistance of non-small cell lung cancer by regulating ROS level under hypoxia condition.Int J Radiat Biol,2017,93:764-70
[38]Porta C,Paglino C,Mosca A.Targeting PI3K/Akt/mTORsignaling in cancer.Front Oncol,2014,4:64
[39]Wang L,Wang R.Effect of rapamycin(RAPA)on the growth of lung cancer and its mechanism in mice with A549.Int J Clin Exp Pathol,2015,8:9208-13
[40]Li YY,Lam SK,Zheng CY,et al.The effect of tumor microenvironment on autophagy and sensitivity to targeted therapy in EGFR-mutated lung adenocarcinoma.J Cancer,2015,6:382-6
[41]Liu JT,Li WC,Gao S,et al.Autophagy inhibition overcomes the antagonistic effect between gefitinib and cisplatin in epidermal growth factor receptor mutant non--small-cell lung cancer cells.Clin Lung Cancer,2015,16:e55-66
[42]Jiang XM,Xu YL,Huang MY,et al.Osimertinib(AZD9291)decreases programmed death ligand-1 in EGFR-mutated non-small cell lung cancer cells.Acta Pharmacol Sin,2017,38:1512-20
[43]Faber AC,Li D,Song Y,et al.Differential induction of apoptosis in HER2 and EGFR addicted cancers following PI3K inhibition.Proc Natl Acad Sci USA,2009,106:19503-8
[44]Jin HO,Lee YH,Park JA,et al.Blockage of Stat3 enhances the sensitivity of NSCLC cells to PI3K/mTOR inhibition.Biochem Biophys Res Commun,2014,444:502-8
[45]Xu CX,Zhao L,Yue P,et al.Augmentation of NVP-BEZ235's anticancer activity against human lung cancer cells by blockage of autophagy.Cancer Biol Ther,2011,12:549-55
[46]Yip PY.Phosphatidylinositol 3-kinase-AKT-mammalian target of rapamycin(PI3K-Akt-mTOR)signaling pathway in non-small cell lung cancer.Transl Lung Cancer Res,2015,4:165-76
[47]Gurpinar E,Grizzle WE,Shacka JJ,et al.A novel sulindac derivative inhibits lung adenocarcinoma cell growth through suppression of Akt/mTOR signaling and induction of autophagy.Mol Cancer Ther,2013,12:663-74
[48]Zhao T,Wang HJ,Zhao WW,et al.Gambogic acid improves non-small cell lung cancer progression by inhibition of mTOR signaling pathway.Kaohsiung J Med Sci,2017,33:543-9
[49]Wang A,Wang J,Zhang S,et al.Curcumin inhibits the development of non-small cell lung cancer by inhibiting autophagy and apoptosis.Exp Ther Med,2017,14:5075-80
[50]Liu F,Gao S,Yang Y,et al.Antitumor activity of curcumin by modulation of apoptosis and autophagy in human lung cancer A549 cells through inhibiting PI3K/Akt/mTORpathway.Oncol Rep,2018,39:1523-31
[51]He H,Sun YP,Zheng L,et al.Steroidal saponins from Paris polyphylla induce apoptotic cell death and autophagy in A549 human lung cancer cells.Asian Pac J Cancer Prev,2015,16:1169-73
[2]Zhou C,Yao LD.Strategies to improve outcomes of patients with EGFR-mutant non-small cell lung cancer:review of the literature.J Thorac Oncol,2016,11:174-86
[3]Takeshige K,Baba M,Tsuboi S,et al.Autophagy in yeast demonstrated with proteinase-deficient mutants and conditions for its induction.J Cell Biol,1992,119:301-11
[4]Wen X,Klionsky DJ.An overview of macroautophagy in yeast.J Mol Biol,2016,428:1681-99
[5]Sahu R,Kaushik S,Clement CC,et al.Microautophagy of cytosolic proteins by late endosomes.Dev Cell,2011,20:131-9
[6]Patel AS,Morse D,Choi AM.Regulation and functional significance of autophagy in respiratory cell biology and disease.Am J Respir Cell Mol Biol,2013,48:1-9
[7]Wong PM,Puente C,Ganley IG,et al.The ULK1complex:sensing nutrient signals for autophagy activation.Autophagy,2013,9:124-37
[8]Puente C,Hendrickson RC,Jiang X.Nutrient-regulated phosphorylation of ATG13 inhibits starvation-induced autophagy.J Biol Chem,2016,291:6026-35
[9]Saleiro D,Mehrotra S,Kroczynska B,et al.Central role of ULK1 in type I interferon signaling.Cell Rep,2015,11:605-17
[10]Shimobayashi M,Hall MN.Making new contacts:the mTOR network in metabolism and signalling crosstalk.Nat Rev Mol Cell Biol,2014,15:155-62
[11]Egan DF,Chun MG,Vamos M,et al.Small molecule inhibition of the autophagy kinase ULK1 and identification of ULK1 substrates.Mol Cell,2015,59:285-97
[12]Park JM,Jung CH,Seo M,et al.The ULK1 complex mediates MTORC1 signaling to the autophagy initiation machinery via binding and phosphorylating ATG14.Autophagy,2016,12:547-64
[13]Hardie DG.AMPK--sensing energy while talking to other signaling pathways.Cell Metab,2014,20:939-52
[14]Hoyer-Hansen M,Bastholm L,Szyniarowski P,et al.Control of macroautophagy by calcium,calmodulindependent kinase kinase-β,and Bcl-2.Mol Cell,2007,25:193-205
[15]Wei Y,Zou Z,Becker N,et al.EGFR-mediated Beclin 1phosphorylation in autophagy suppression,tumor progression,and tumor chemoresistance.Cell,2013,154:1269-84
[16]Nazio F,Strappazzon F,Antonioli M,et al.mTOR inhibits autophagy by controlling ULK1 ubiquitylation,selfassociation and function through AMBRA1 and TRAF6.Nat Cell Biol,2013,15:406-16
[17]Liang XH,Jackson S,Seaman M,et al.Induction of autophagy and inhibition of tumorigenesis by beclin 1.Nature,1999,402:672-6
[18]Yue Z,Jin S,Yang C,et al.Beclin 1,an autophagy gene essential for early embryonic development,is a haploinsufficient tumor suppressor.Proc Natl Acad Sci USA,2003,100:15077-82
[19]White E.The role for autophagy in cancer.J Clin Invest,2015,125:42-6
[20]Mathew R,White E.Autophagy in tumorigenesis and energy metabolism:friend by day,foe by night.Curr Opin Genet Dev,2011,21:113-9
[21]Mathew R,Karp CM,Beaudoin B,et al.Autophagy suppresses tumorigenesis through elimination of p62.Cell,2009,137:1062-75
[22]Kenific CM,Thorburn A,Debnath J.Autophagy and metastasis:another double-edged sword.Curr Opin Cell Biol,2010,22:241-5
[23]Sosa MS,Bragado P,Debnath J,et al.Regulation of tumor cell dormancy by tissue microenvironments and autophagy.Adv Exp Med Biol,2013,734:73-89
[24]Guo JY,Chen HY,Mathew R,et al.Activated Ras requires autophagy to maintain oxidative metabolism and tumorigenesis.Genes Dev,2011,25:460-70
[25]Liu G,Pei F,Yang F,et al.Role of autophagy and apoptosis in non-small-cell lung cancer.Int J Mol Sci,2017,18:367
[26]Guo JY,Karsli-Uzunbas G,Mathew R,et al.Autophagy suppresses progression of K-ras-induced lung tumors to oncocytomas and maintains lipid homeostasis.Genes Dev,2013,27:1447-61
[27]Strohecker AM,Guo JY,Karsli-Uzunbas G,et al.Autophagy sustains mitochondrial glutamine metabolism and growth of BrafV600E-driven lung tumors.Cancer Discov,2013,3:1272-85
[28]Zhou Y,Huang N,Wu J,et al.Silencing of NRAGEinduces autophagy via AMPK/Ulk1/Atg13 signaling pathway in NSCLC cells.Tumour Biol,2017,39:1010428317709676
[29]Rothschild SI,Gautschi O,Batliner J,et al.MicroRNA-106a targets autophagy and enhances sensitivity of lung cancer cells to Src inhibitors.Lung Cancer,2017,107:73-83
[30]Cai J,Li R,Xu X,et al.CK1αsuppresses lung tumour growth by stabilizing PTEN and inducing autophagy.Nat Cell Biol,2018,20:465-78
[31]Ramirez M,Rajaram S,Steininger RJ,et al.Diverse drugresistance mechanisms can emerge from drug-tolerant cancer persister cells.Nat Commun,2016,7:10690
[32]Liang C,Zhang X,Wang HM,et al.MicroRNA-18a-5p functions as an oncogene by directly targeting IRF2 in lung cancer.Cell Death Dis,2017,8:e2764
[33]Ye Z,Fang B,Pan J,et al.miR-138 suppresses the proliferation,metastasis and autophagy of non-small cell lung cancer by targeting Sirt1.Oncol Rep,2017,37:3244-52
[34]Mi S,Xiang G,Yuwen D,et al.Inhibition of autophagy by andrographolide resensitizes cisplatin-resistant non-small cell lung carcinoma cells via activation of the Akt/mTORpathway.Toxicol Appl Pharmacol,2016,310:78-86
[35]Yuwen DL,Sheng BB,Liu J,et al.MiR-146a-5p level in serum exosomes predicts therapeutic effect of cisplatin in non-small cell lung cancer.Eur Rev Med Pharmacol Sci,2017,21:2650-8
[36]Zarogoulidis P,Petanidis S,Domvri K,et al.Autophagy inhibition upregulates CD4+tumor infiltrating lymphocyte expression via miR-155 regulation and TRAIL activation.Mol Oncol,2016,10:1516-31
[37]Chen X,Wang P,Guo F,et al.Autophagy enhanced the radioresistance of non-small cell lung cancer by regulating ROS level under hypoxia condition.Int J Radiat Biol,2017,93:764-70
[38]Porta C,Paglino C,Mosca A.Targeting PI3K/Akt/mTORsignaling in cancer.Front Oncol,2014,4:64
[39]Wang L,Wang R.Effect of rapamycin(RAPA)on the growth of lung cancer and its mechanism in mice with A549.Int J Clin Exp Pathol,2015,8:9208-13
[40]Li YY,Lam SK,Zheng CY,et al.The effect of tumor microenvironment on autophagy and sensitivity to targeted therapy in EGFR-mutated lung adenocarcinoma.J Cancer,2015,6:382-6
[41]Liu JT,Li WC,Gao S,et al.Autophagy inhibition overcomes the antagonistic effect between gefitinib and cisplatin in epidermal growth factor receptor mutant non--small-cell lung cancer cells.Clin Lung Cancer,2015,16:e55-66
[42]Jiang XM,Xu YL,Huang MY,et al.Osimertinib(AZD9291)decreases programmed death ligand-1 in EGFR-mutated non-small cell lung cancer cells.Acta Pharmacol Sin,2017,38:1512-20
[43]Faber AC,Li D,Song Y,et al.Differential induction of apoptosis in HER2 and EGFR addicted cancers following PI3K inhibition.Proc Natl Acad Sci USA,2009,106:19503-8
[44]Jin HO,Lee YH,Park JA,et al.Blockage of Stat3 enhances the sensitivity of NSCLC cells to PI3K/mTOR inhibition.Biochem Biophys Res Commun,2014,444:502-8
[45]Xu CX,Zhao L,Yue P,et al.Augmentation of NVP-BEZ235's anticancer activity against human lung cancer cells by blockage of autophagy.Cancer Biol Ther,2011,12:549-55
[46]Yip PY.Phosphatidylinositol 3-kinase-AKT-mammalian target of rapamycin(PI3K-Akt-mTOR)signaling pathway in non-small cell lung cancer.Transl Lung Cancer Res,2015,4:165-76
[47]Gurpinar E,Grizzle WE,Shacka JJ,et al.A novel sulindac derivative inhibits lung adenocarcinoma cell growth through suppression of Akt/mTOR signaling and induction of autophagy.Mol Cancer Ther,2013,12:663-74
[48]Zhao T,Wang HJ,Zhao WW,et al.Gambogic acid improves non-small cell lung cancer progression by inhibition of mTOR signaling pathway.Kaohsiung J Med Sci,2017,33:543-9
[49]Wang A,Wang J,Zhang S,et al.Curcumin inhibits the development of non-small cell lung cancer by inhibiting autophagy and apoptosis.Exp Ther Med,2017,14:5075-80
[50]Liu F,Gao S,Yang Y,et al.Antitumor activity of curcumin by modulation of apoptosis and autophagy in human lung cancer A549 cells through inhibiting PI3K/Akt/mTORpathway.Oncol Rep,2018,39:1523-31
[51]He H,Sun YP,Zheng L,et al.Steroidal saponins from Paris polyphylla induce apoptotic cell death and autophagy in A549 human lung cancer cells.Asian Pac J Cancer Prev,2015,16:1169-73