自噬在肺癌中的研究进展
|
摘要
肺癌全称为原发性支气管肺癌(primary bronchogenic carcinoma),是最常见恶性肿瘤之一。尽管近年来各种新的治疗手段不断问世,肺癌患者的整体预后仍不理想,5年生存率仅为18%左右,亟需寻找更好的治疗手段。自噬(autophagy)一词源自于古代希腊语"auto"(自我)与"phagein"(吞噬)的结合,是真核生物中高度保守的依赖于溶酶体的降解过程,细胞可通过分解自身受损或多余的细胞器和细胞质来维持内环境的稳态。随着对自噬研究的深入,越来越多证据表明,自噬在肺癌的发生发展中起极为关键的作用,有望成为肺癌治疗的新靶点。本文就自噬的机制及自噬在肺癌中的研究进展进行综述。
Lung cancer is called primary bronchogenic carcinoma, and is one of the most common malignant tumors. Despite the continuous emergence of new treatments in recent years, the overall prognosis of lung cancer patients was still unsatisfactory and the five-year survival rate is only about 18%. Hence, it's urgent to find better treatments. The word ''autophagy'' is derived from the combination of the ancient Greek "auto" and "phagein". It is a highly conserved lysosomal-dependent degradation process in eukaryotes, in which cells can maintain homeostasis by degrading their own damaged or redundant organelles and cytoplasm. With the deepening of autophagy research, more and more evidence indicate that autophagy plays a crucial role in the development of lung cancer and is expected to become a new target for lung cancer treatment. This review summaries the mechanism of autophagy and the research progress of autophagy in lung cancer.
Lung cancer is called primary bronchogenic carcinoma, and is one of the most common malignant tumors. Despite the continuous emergence of new treatments in recent years, the overall prognosis of lung cancer patients was still unsatisfactory and the five-year survival rate is only about 18%. Hence, it's urgent to find better treatments. The word ''autophagy'' is derived from the combination of the ancient Greek "auto" and "phagein". It is a highly conserved lysosomal-dependent degradation process in eukaryotes, in which cells can maintain homeostasis by degrading their own damaged or redundant organelles and cytoplasm. With the deepening of autophagy research, more and more evidence indicate that autophagy plays a crucial role in the development of lung cancer and is expected to become a new target for lung cancer treatment. This review summaries the mechanism of autophagy and the research progress of autophagy in lung cancer.
引文
[1]CLARK SL Jr.Cellular differentiation in the kidneys of newborn mice studies with the electron microscope[J].J Biophys Biochem Cytol,1957,3(3):349-362.
[2]NOVIKOFF AB,ESSNER E.Cytolysomes and mitochondrial degeneration[J].J Cell Biol,1962,15:140-146.
[3]MIZUSHIMA N.A brief history of autophagy from cell biology to physiology and disease[J].Nat Cell Biol,2018,20(5):521-527.
[4]LEVINE B,KROEMER G.Autophagy in the pathogenesis of disease[J].Cell,2008,132(1):27-42.
[5]KANZAWA T,KONDO Y,ITO H,et al.Induction of autophagic cell death in malignant glioma cells by arsenic trioxide[J].Cancer Res,2003.63(9):2103-2108.
[6]YANG Z,KLIONSKY DJ.Eaten alive:a history of macroautophagy[J].Nat Cell Biol,2010,12(9):814-822.
[7]NODA NN,INAGAKI F.Mechanisms of autophagy[J].Annu Rev Biophys,2015,44:101-122.
[8]ZACHARI M,GANLEY IG.The mammalian ULK1 complex and autophagy initiation[J].Essays Biochem,2017,61(6):585-596.
[9]RABANAL-RUIZ Y,OTTEN EG,KOROLCHUK VI.mTORC1 as the main gateway to autophagy[J].Essays Biochem,2017,61(6):565-584.
[10]KIM J,KUNDU M,VIOLLET B,GUAN KL.AMPK and m TORregulate autophagy through direct phosphorylation of Ulk1[J].Nat Cell Biol,2011,13(2):132-141.
[11]SIMONSEN A,TOOZE SA.Coordination of membrane events during autophagy by multiple class III PI3-kinase complexes[J].J Cell Biol,2009,186(6):773-782.
[12]ARAKI Y,KU WC,AKIOKA M,et al.Atg38 is required for autophagy-specific phosphatidylinositol 3-kinase complex integrity[J].JCell Biol,2013,203(2):299-313.
[13]MIZUSHIMA N,NODA T,OHSUMI Y.Apg16p is required for the function of the Apg12p-Apg5p conjugate in the yeast autophagy pathway[J].EMBO J,1999,18(14):3888-3896.
[14]MIZUSHIMA N,SUGITA H,YOSHIMORI T,et al.A protein conjugation system essential for autophagy[J].J Biol Chem,1998,273(51):33889-33892.
[15]KIRISAKO T,ICHIMURA Y,OKADA H,et al.The reversible modification regulates the membrane-binding state of Apg8/Aut7 essential for autophagy and the cytoplasm to vacuole targeting pathway[J].JCell Biol,2000,151(2):263-276.
[16]ICHIMURA Y,KIRISAKO T,TAKAO T,et al.A ubiquitin-like system mediates protein lipidation[J].Nature,2000,408(6811):488-492.
[17]HANADA T,NODA NN,SATOMI Y,et al.The Atg12-Atg5 conjugate has a novel E3-like activity for protein lipidation in autophagy[J].J Biol Chem,2007,282(52):37298-37302.
[18]QU X,YU J,BHAGAT G,et al.Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene[J].J Clin Invest,2003,112(12):1809-1820.
[19]DEGENHARDT K,MATHEW R,BEAUDOIN B,et al.Autophagy promotes tumor cell survival and restricts necrosis,inflammation,and tumorigenesis[J].Cancer Cell,2006,10(1):51-64.
[20]HE J,YU JJ,XU Q,et al.Downregulation of ATG14 by EGR1-MIR152sensitizes ovarian cancer cells to cisplatin-induced apoptosis by inhibiting cyto-protective autophagy[J].Autophagy,2015,11(2):373-384.
[21]RAO S,TORTOLA L,PERLOT T,et al.A dual role for autophagy in a murine model of lung cancer[J].Nat Commun,2014,5:3056.
[22]STROHECKER AM,GUO JY,KARSLI-UZUNBAS G,et al.Autophagy sustains mitochondrial glutamine metabolism and growth of BrafV600E-driven lung tumors[J].Cancer Discov,2013,3(11):1272-1285.
[23]LIU J,LIU L,TIAN Z,et al.In silico discovery of a small molecule suppressing lung carcinoma A549 cells proliferation and inducing autophagy via mTOR pathway inhibition[J].Mol Pharm,2018,15(11):5427-5436.
[24]YANG Z,SU Z,DEWITT JP,et al.Fluvastatin prevents lung adenocarcinoma bone metastasis by triggering autophagy[J].EBioMedicine,2017,19:49-59.
[25]XUE Y,HAN H,WU L,et al.i ASPP facilitates tumor growth by promoting mTOR-dependent autophagy in human non-small-cell lung cancer[J].Cell Death Dis,2017,8(10):e3150.
[26]CIRCU M,CARDELLI J,BARR MP,et al.Modulating lysosomal function through lysosome membrane permeabilization or autophagy suppression restores sensitivity to cisplatin in refractory non-small-cell lung cancer cells[J].PLo S One,2018,13(5):e0197016.
[27]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/mTOR pathway[J].Toxicol Appl Pharmacol,2016,310:78-86.
[28]REN J,LIU T,HAN Y,et al.GSK-3βinhibits autophagy and enhances radiosensitivity in non-small cell lung cancer[J].Diagn Pathol,2018,13(1):33.
[29]WANG Y,LI N,JIANG W,et al.Mutant LKB1 confers enhanced radiosensitization in combination with trametinib in KRAS-mutant non-small cell lung cancer[J].Clin Cancer Res,2018,24(22):5744-5756.
[30]ANASTASIADOU E,JACOB LS,SLACK FJ.Non-coding RNA networks in cancer[J].Nat Rev Cancer,2018,18(1):5-18.
[31]ROTHSCHILD SI,GAUTSCHI O,BATLINER J,et al.MicroR-NA-106a targets autophagy and enhances sensitivity of lung cancer cells to Src inhibitors[J].Lung Cancer,2017,107:73-83.
[32]HUA L,ZHU G,WEI J.MicroRNA-1 overexpression increases chemosensitivity of non-small cell lung cancer cells by inhibiting autophagy related 3-mediated autophagy[J].Cell Biol Int,2018.doi:10.1002/cbin.10995.
[33]HUANG FX,CHEN HJ,ZHENG FX,et al.LncRNA BLACAT1 is involved in chemoresistance of non-small cell lung cancer cells by regulating autophagy[J].Int J Oncol,2019,54(1):339-347.
[2]NOVIKOFF AB,ESSNER E.Cytolysomes and mitochondrial degeneration[J].J Cell Biol,1962,15:140-146.
[3]MIZUSHIMA N.A brief history of autophagy from cell biology to physiology and disease[J].Nat Cell Biol,2018,20(5):521-527.
[4]LEVINE B,KROEMER G.Autophagy in the pathogenesis of disease[J].Cell,2008,132(1):27-42.
[5]KANZAWA T,KONDO Y,ITO H,et al.Induction of autophagic cell death in malignant glioma cells by arsenic trioxide[J].Cancer Res,2003.63(9):2103-2108.
[6]YANG Z,KLIONSKY DJ.Eaten alive:a history of macroautophagy[J].Nat Cell Biol,2010,12(9):814-822.
[7]NODA NN,INAGAKI F.Mechanisms of autophagy[J].Annu Rev Biophys,2015,44:101-122.
[8]ZACHARI M,GANLEY IG.The mammalian ULK1 complex and autophagy initiation[J].Essays Biochem,2017,61(6):585-596.
[9]RABANAL-RUIZ Y,OTTEN EG,KOROLCHUK VI.mTORC1 as the main gateway to autophagy[J].Essays Biochem,2017,61(6):565-584.
[10]KIM J,KUNDU M,VIOLLET B,GUAN KL.AMPK and m TORregulate autophagy through direct phosphorylation of Ulk1[J].Nat Cell Biol,2011,13(2):132-141.
[11]SIMONSEN A,TOOZE SA.Coordination of membrane events during autophagy by multiple class III PI3-kinase complexes[J].J Cell Biol,2009,186(6):773-782.
[12]ARAKI Y,KU WC,AKIOKA M,et al.Atg38 is required for autophagy-specific phosphatidylinositol 3-kinase complex integrity[J].JCell Biol,2013,203(2):299-313.
[13]MIZUSHIMA N,NODA T,OHSUMI Y.Apg16p is required for the function of the Apg12p-Apg5p conjugate in the yeast autophagy pathway[J].EMBO J,1999,18(14):3888-3896.
[14]MIZUSHIMA N,SUGITA H,YOSHIMORI T,et al.A protein conjugation system essential for autophagy[J].J Biol Chem,1998,273(51):33889-33892.
[15]KIRISAKO T,ICHIMURA Y,OKADA H,et al.The reversible modification regulates the membrane-binding state of Apg8/Aut7 essential for autophagy and the cytoplasm to vacuole targeting pathway[J].JCell Biol,2000,151(2):263-276.
[16]ICHIMURA Y,KIRISAKO T,TAKAO T,et al.A ubiquitin-like system mediates protein lipidation[J].Nature,2000,408(6811):488-492.
[17]HANADA T,NODA NN,SATOMI Y,et al.The Atg12-Atg5 conjugate has a novel E3-like activity for protein lipidation in autophagy[J].J Biol Chem,2007,282(52):37298-37302.
[18]QU X,YU J,BHAGAT G,et al.Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene[J].J Clin Invest,2003,112(12):1809-1820.
[19]DEGENHARDT K,MATHEW R,BEAUDOIN B,et al.Autophagy promotes tumor cell survival and restricts necrosis,inflammation,and tumorigenesis[J].Cancer Cell,2006,10(1):51-64.
[20]HE J,YU JJ,XU Q,et al.Downregulation of ATG14 by EGR1-MIR152sensitizes ovarian cancer cells to cisplatin-induced apoptosis by inhibiting cyto-protective autophagy[J].Autophagy,2015,11(2):373-384.
[21]RAO S,TORTOLA L,PERLOT T,et al.A dual role for autophagy in a murine model of lung cancer[J].Nat Commun,2014,5:3056.
[22]STROHECKER AM,GUO JY,KARSLI-UZUNBAS G,et al.Autophagy sustains mitochondrial glutamine metabolism and growth of BrafV600E-driven lung tumors[J].Cancer Discov,2013,3(11):1272-1285.
[23]LIU J,LIU L,TIAN Z,et al.In silico discovery of a small molecule suppressing lung carcinoma A549 cells proliferation and inducing autophagy via mTOR pathway inhibition[J].Mol Pharm,2018,15(11):5427-5436.
[24]YANG Z,SU Z,DEWITT JP,et al.Fluvastatin prevents lung adenocarcinoma bone metastasis by triggering autophagy[J].EBioMedicine,2017,19:49-59.
[25]XUE Y,HAN H,WU L,et al.i ASPP facilitates tumor growth by promoting mTOR-dependent autophagy in human non-small-cell lung cancer[J].Cell Death Dis,2017,8(10):e3150.
[26]CIRCU M,CARDELLI J,BARR MP,et al.Modulating lysosomal function through lysosome membrane permeabilization or autophagy suppression restores sensitivity to cisplatin in refractory non-small-cell lung cancer cells[J].PLo S One,2018,13(5):e0197016.
[27]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/mTOR pathway[J].Toxicol Appl Pharmacol,2016,310:78-86.
[28]REN J,LIU T,HAN Y,et al.GSK-3βinhibits autophagy and enhances radiosensitivity in non-small cell lung cancer[J].Diagn Pathol,2018,13(1):33.
[29]WANG Y,LI N,JIANG W,et al.Mutant LKB1 confers enhanced radiosensitization in combination with trametinib in KRAS-mutant non-small cell lung cancer[J].Clin Cancer Res,2018,24(22):5744-5756.
[30]ANASTASIADOU E,JACOB LS,SLACK FJ.Non-coding RNA networks in cancer[J].Nat Rev Cancer,2018,18(1):5-18.
[31]ROTHSCHILD SI,GAUTSCHI O,BATLINER J,et al.MicroR-NA-106a targets autophagy and enhances sensitivity of lung cancer cells to Src inhibitors[J].Lung Cancer,2017,107:73-83.
[32]HUA L,ZHU G,WEI J.MicroRNA-1 overexpression increases chemosensitivity of non-small cell lung cancer cells by inhibiting autophagy related 3-mediated autophagy[J].Cell Biol Int,2018.doi:10.1002/cbin.10995.
[33]HUANG FX,CHEN HJ,ZHENG FX,et al.LncRNA BLACAT1 is involved in chemoresistance of non-small cell lung cancer cells by regulating autophagy[J].Int J Oncol,2019,54(1):339-347.