自噬在肺癌中的研究进展
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摘要
自噬是将细胞内大分子,损伤细胞器及代谢产物运送到溶酶体发生降解,并产生可供细胞再利用的能源物质过程。目前研究最广泛的是巨自噬和线粒体自噬。肺癌患病率高且病死率居高不下,寻找更为有效的治疗方法和靶向药物意义重大。自噬与肺癌关系密切,自噬在肺癌的发生发展、治疗以及治疗耐药等过程中发挥重要作用,同时随着外泌体研究的兴起,人们发现外泌体参与机体多种病理生理过程,包括自噬过程,通过与自噬的交互作用,影响肺癌进展。而通过靶向调节肺癌细胞内自噬过程,可以影响肺癌进展,从而用于肺癌的治疗。
Autophagy is the process of transporting macromolecules,damaged organelles and metabolites into lysosomes to degrade and produce energy materials for cell reuse. At present,macroautophagy and mitochondrial autophagy are the most widely studied. Lung cancer has a high morbidity and mortality,therefore it is of great significance to find more effective treatments and targeted drugs. Autophagy is closely related to lung cancer,playing an important role in the occurrence,development,treatment and drug resistance of lung cancer. With the rise of exosome research,it has been found that exosomes participate in many pathophysiological processes,including autophagy,and affect the progress of lung cancer through interaction with autophagy. Targeted regulation of autophagy in lung cancer cells can affect the progress of lung cancer,therefore can be used in the treatment.
Autophagy is the process of transporting macromolecules,damaged organelles and metabolites into lysosomes to degrade and produce energy materials for cell reuse. At present,macroautophagy and mitochondrial autophagy are the most widely studied. Lung cancer has a high morbidity and mortality,therefore it is of great significance to find more effective treatments and targeted drugs. Autophagy is closely related to lung cancer,playing an important role in the occurrence,development,treatment and drug resistance of lung cancer. With the rise of exosome research,it has been found that exosomes participate in many pathophysiological processes,including autophagy,and affect the progress of lung cancer through interaction with autophagy. Targeted regulation of autophagy in lung cancer cells can affect the progress of lung cancer,therefore can be used in the treatment.
引文
[1]Guo JY,White E.Autophagy,Metabolism,and Cancer[J].Cold Spring Harb Symp Quant Biol,2016,81:73-78.
[2]Lin L,Baehrecke EH.Autophagy,cell death,and cancer[J].Mol Cell Oncol,2015,2(3):e985913.
[3]Guo JY,Chen HY,Matherr R,et al.Activated Ras requires autophagy to maintain oxidative metabolism and tumorigenesis[J].Genes Dev,2011,25(5):460-470.
[4]Mathew R,Karp CM,Beaudoin B,et al.Autophagy suppresses tumorigenesis through elimination of p62[J].Cell,2009,137(6):1062-1075.
[5]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.
[6]Hong QY,Wu GM,Qian GS,et al.Prevention and management of lung cancer in China[J].Cancer,2015,121 Suppl 17:3080-3088.
[7]Siegel RL,Miller KD,Jemal A.Cancer statistics,2016[J].CACancer J Clin,2016,66(1):7-30.
[8]Nakahira K,Pabon Porras MA,Choi AM.Autophagy in Pulmonary Diseases[J].Am J Respir Crit Care Med,2016,194(10):1196-1207.
[9]Doria A,Gatto M,Puzzi L.Autophagy in human health and disease[J].N Engl J Med,2013,368(19):1845.
[10]Takura E,Mizushima N.p62 Targeting to the autophagosome formation site requires self-oligomerization but not LC3 binding[J].J Cell Biol,2011,192(1):17-27.
[11]Hite E.Deconvoluting the context-dependent role for autophagy in cancer[J].Nat Rev Cancer,2012,12(6):401-410.
[12]Rao S,Yang H,Penninger JM,et al.Autophagy in non-small cell lung carcinogenesis:A positive regulator of antitumor immunosurveillance[J].Autophagy,2014,10(3):529-531.
[13]Guo JY,Karsli-Uzunbas G,Mathew R,et al.Autophagy suppresses progression of K-ras-induced lung tumors to oncocytomas and maintains lipid homeostasis[J].Genes Dev,2013,27(13):1447-1461.
[14]Schlafli AM,Adans O,Galvan JA,et al.Prognostic value of the autophagy markers LC3 and p62/SQSTM1 in early-stage non-small cell lung cancer[J].Oncotarget,2016,7(26):39544-39555.
[15]Zheng LW,Li Y,Ge D,et al.Synthesis of novel oxime-containing pyrazole derivatives and discovery of regulators for apoptosis and autophagy in A549 lung cancer cells[J].Bioorg Med Chem Lett,2010,20(16):4766-4770.
[16]Choi CH,Jung YK,Oh SH.Selective induction of catalase-mediated autophagy by dihydrocapsaicin in lung cell lines[J].Free Radic Biol Med,2010,49(2):245-257.
[17]Chen J,Zhang L,Zhou H,et al.Inhibition of autophagy promotes cisplatin-induced apoptotic cell death through Atg5 and Beclin 1in A549 human lung cancer cells[J].Mol Med Rep,2018,17(5):6859-6865.
[18]Leung ELH,Luo LX,Liu ZQ,et al.Inhibition of KRAS-dependent lung cancer cell growth by deltarasin:Blockage of autophagy increases its cytotoxicity[J].Cell Death Dis,2018,9(2):216.
[19]Su Z,Wang K,Li R,et al.Overexpression of RBM5 induces autophagy in human lung adenocarcinoma cells[J].World J Surg Oncol,2016,14:57.
[20]Yao W,Yue P,Zhang G,et al.Enhancing therapeutic efficacy of the MEK inhibitor,MEK162,by blocking autophagy or inhibiting PI3K/Akt signaling in human lung cancer cells[J].Cancer Lett,2015,364(1):70-78.
[21]Ding WX,Yin XM.Mitophagy:Mechanisms,pathophysiological roles,and analysis[J].Biol Chem,2012,393(7):547-564.
[22]Narendra DP,Youle RJ.Targeting mitochondrial dysfunction:Role for PINK1 and Parkin in mitochondrial quality control[J].Antioxid Redox Signal,2011,14(10):1929-1938.
[23]Villa E,Proics E,Rubio-Patino C,et al.Parkin-Independent Mitophagy Controls Chemotherapeutic Response in Cancer Cells[J].Cell Rep,2017,20(12):2846-2859.
[24]杨莹.肺癌干细胞的氧化磷酸化异常与线粒体自噬关系的研究[D].杭州:浙江大学,2016.
[25]夏茂.线粒体自噬调控麻疹病毒疫苗株在非小细胞肺癌中的溶瘤作用及机制研究[D].南京:南京大学,2015.
[26]Chang SH,Lee AY,Yu KN,et al.Dihydroergotamine Tartrate Induces Lung Cancer Cell Death through Apoptosis and Mitophagy[J].Chemotherapy,2016,61(6):304-312.
[27]王琎,陈建英.细胞外囊泡研究新进展[J].中国组织工程研究,2017,21(4):621-626.
[28]余沈桐,韦伊芳,张健.细胞外囊泡与肿瘤相关性的研究[J].现代肿瘤医学,2016,24(8):1302-1306.
[29]Boyiadzis M,Whiteside TL.Information transfer by exosomes:Anew frontier in hematologic malignancies[J].Blood Rev,2015,29(5):281-290.
[30]陈奇,徐彬,毛建文.大鼠血清外泌体对MCF-7细胞自噬的影响[J/CD].中西医结合心血管病电子杂志,2018,6(7):176-177.
[31]李川,刘卓刚,胡荣.外泌体在白血病中的研究进展[J].现代肿瘤医学,2018,26(12):1946-1950.
[32]Song M,Wang Y,Shang ZF,et al.Bystander autophagy mediated by radiation-induced exosomal miR-7-5p in non-targeted human bronchial epithelial cells[J].Sci Rep,2016,6:30165.
[33]胡洪林.miR-7-5p通过靶向抑制EGFR表达减弱人非小细胞肺癌的增殖和侵袭能力[J].临床肺科杂志,2018,23(6):1005-1009.
[34]刘承一,肇爽,白璐,等.miR-7-5p靶向调控EGFR对非小细胞肺癌细胞增殖侵袭的影响[J].山东医药,2017,57(45):36-38.
[35]Guo H,Chitiprolu M,Roncevic L,et al.Atg5 Disassociates the V1V0-ATPase to Promote Exosome Production and Tumor Metastasis Independent of Canonical Macroautophagy[J].Dev Cell,2017,43(6):716-730.e717.
[36]Li XQ,Liu JT,Fan LL,et al.Exosomes derived from gefitinibtreated EGFR-mutant lung cancer cells alter cisplatin sensitivity via up-regulating autophagy[J].Oncotarget,2016,7(17):24585-24595.
[37]NCCN.NCCN Guidelines for Patients:Lung Cancer[EB/OL].https://www.nccn.org/patients/guidelines/lung-nsclc,2018-09-28.
[38]Zois CE,Giatromanolaki A,Kainulainen H,et al.Lung autophagic response following exposure of mice to whole body irradiation,with and without amifostine[J].Biochem Biophys Res Commun,2011,404(1):552-558.
[39]Gewirtz DA.The Challenge of Developing Autophagy Inhibition as a Therapeutic Strategy[J].Cancer Res,2016,76(19):5610-5614.
[40]Nazim UM,Moon JH,Lee JH,et al.Activation of autophagy flux by metformin downregulates cellular FLICE-like inhibitory protein and enhances TRAIL-induced apoptosis[J].Oncotarget,2016,7(17):23468-23481.
[41]Han W,Pan H,Chen Y,et al.EGFR tyrosine kinase inhibitors activate autophagy as a cytoprotective response in human lung cancer cells[J].PLo S One,2011,6(6):e18691.
[42]Chen T,Ren H,Thakur A,et al.Decreased Level of Klotho Contributes to Drug Resistance in Lung Cancer Cells:Involving in Klotho-Mediated Cell Autophagy[J].DNA Cell Biol,2016,35(12):751-757.
[43]Yu XS,Du J,Fan YJ,et al.Activation of endoplasmic reticulum stress promotes autophagy and apoptosis and reverses chemoresistance of human small cell lung cancer cells by inhibiting the PI3K/AKT/m TOR signaling pathway[J].Oncotarget,2016,7(47):76827-76839.
[2]Lin L,Baehrecke EH.Autophagy,cell death,and cancer[J].Mol Cell Oncol,2015,2(3):e985913.
[3]Guo JY,Chen HY,Matherr R,et al.Activated Ras requires autophagy to maintain oxidative metabolism and tumorigenesis[J].Genes Dev,2011,25(5):460-470.
[4]Mathew R,Karp CM,Beaudoin B,et al.Autophagy suppresses tumorigenesis through elimination of p62[J].Cell,2009,137(6):1062-1075.
[5]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.
[6]Hong QY,Wu GM,Qian GS,et al.Prevention and management of lung cancer in China[J].Cancer,2015,121 Suppl 17:3080-3088.
[7]Siegel RL,Miller KD,Jemal A.Cancer statistics,2016[J].CACancer J Clin,2016,66(1):7-30.
[8]Nakahira K,Pabon Porras MA,Choi AM.Autophagy in Pulmonary Diseases[J].Am J Respir Crit Care Med,2016,194(10):1196-1207.
[9]Doria A,Gatto M,Puzzi L.Autophagy in human health and disease[J].N Engl J Med,2013,368(19):1845.
[10]Takura E,Mizushima N.p62 Targeting to the autophagosome formation site requires self-oligomerization but not LC3 binding[J].J Cell Biol,2011,192(1):17-27.
[11]Hite E.Deconvoluting the context-dependent role for autophagy in cancer[J].Nat Rev Cancer,2012,12(6):401-410.
[12]Rao S,Yang H,Penninger JM,et al.Autophagy in non-small cell lung carcinogenesis:A positive regulator of antitumor immunosurveillance[J].Autophagy,2014,10(3):529-531.
[13]Guo JY,Karsli-Uzunbas G,Mathew R,et al.Autophagy suppresses progression of K-ras-induced lung tumors to oncocytomas and maintains lipid homeostasis[J].Genes Dev,2013,27(13):1447-1461.
[14]Schlafli AM,Adans O,Galvan JA,et al.Prognostic value of the autophagy markers LC3 and p62/SQSTM1 in early-stage non-small cell lung cancer[J].Oncotarget,2016,7(26):39544-39555.
[15]Zheng LW,Li Y,Ge D,et al.Synthesis of novel oxime-containing pyrazole derivatives and discovery of regulators for apoptosis and autophagy in A549 lung cancer cells[J].Bioorg Med Chem Lett,2010,20(16):4766-4770.
[16]Choi CH,Jung YK,Oh SH.Selective induction of catalase-mediated autophagy by dihydrocapsaicin in lung cell lines[J].Free Radic Biol Med,2010,49(2):245-257.
[17]Chen J,Zhang L,Zhou H,et al.Inhibition of autophagy promotes cisplatin-induced apoptotic cell death through Atg5 and Beclin 1in A549 human lung cancer cells[J].Mol Med Rep,2018,17(5):6859-6865.
[18]Leung ELH,Luo LX,Liu ZQ,et al.Inhibition of KRAS-dependent lung cancer cell growth by deltarasin:Blockage of autophagy increases its cytotoxicity[J].Cell Death Dis,2018,9(2):216.
[19]Su Z,Wang K,Li R,et al.Overexpression of RBM5 induces autophagy in human lung adenocarcinoma cells[J].World J Surg Oncol,2016,14:57.
[20]Yao W,Yue P,Zhang G,et al.Enhancing therapeutic efficacy of the MEK inhibitor,MEK162,by blocking autophagy or inhibiting PI3K/Akt signaling in human lung cancer cells[J].Cancer Lett,2015,364(1):70-78.
[21]Ding WX,Yin XM.Mitophagy:Mechanisms,pathophysiological roles,and analysis[J].Biol Chem,2012,393(7):547-564.
[22]Narendra DP,Youle RJ.Targeting mitochondrial dysfunction:Role for PINK1 and Parkin in mitochondrial quality control[J].Antioxid Redox Signal,2011,14(10):1929-1938.
[23]Villa E,Proics E,Rubio-Patino C,et al.Parkin-Independent Mitophagy Controls Chemotherapeutic Response in Cancer Cells[J].Cell Rep,2017,20(12):2846-2859.
[24]杨莹.肺癌干细胞的氧化磷酸化异常与线粒体自噬关系的研究[D].杭州:浙江大学,2016.
[25]夏茂.线粒体自噬调控麻疹病毒疫苗株在非小细胞肺癌中的溶瘤作用及机制研究[D].南京:南京大学,2015.
[26]Chang SH,Lee AY,Yu KN,et al.Dihydroergotamine Tartrate Induces Lung Cancer Cell Death through Apoptosis and Mitophagy[J].Chemotherapy,2016,61(6):304-312.
[27]王琎,陈建英.细胞外囊泡研究新进展[J].中国组织工程研究,2017,21(4):621-626.
[28]余沈桐,韦伊芳,张健.细胞外囊泡与肿瘤相关性的研究[J].现代肿瘤医学,2016,24(8):1302-1306.
[29]Boyiadzis M,Whiteside TL.Information transfer by exosomes:Anew frontier in hematologic malignancies[J].Blood Rev,2015,29(5):281-290.
[30]陈奇,徐彬,毛建文.大鼠血清外泌体对MCF-7细胞自噬的影响[J/CD].中西医结合心血管病电子杂志,2018,6(7):176-177.
[31]李川,刘卓刚,胡荣.外泌体在白血病中的研究进展[J].现代肿瘤医学,2018,26(12):1946-1950.
[32]Song M,Wang Y,Shang ZF,et al.Bystander autophagy mediated by radiation-induced exosomal miR-7-5p in non-targeted human bronchial epithelial cells[J].Sci Rep,2016,6:30165.
[33]胡洪林.miR-7-5p通过靶向抑制EGFR表达减弱人非小细胞肺癌的增殖和侵袭能力[J].临床肺科杂志,2018,23(6):1005-1009.
[34]刘承一,肇爽,白璐,等.miR-7-5p靶向调控EGFR对非小细胞肺癌细胞增殖侵袭的影响[J].山东医药,2017,57(45):36-38.
[35]Guo H,Chitiprolu M,Roncevic L,et al.Atg5 Disassociates the V1V0-ATPase to Promote Exosome Production and Tumor Metastasis Independent of Canonical Macroautophagy[J].Dev Cell,2017,43(6):716-730.e717.
[36]Li XQ,Liu JT,Fan LL,et al.Exosomes derived from gefitinibtreated EGFR-mutant lung cancer cells alter cisplatin sensitivity via up-regulating autophagy[J].Oncotarget,2016,7(17):24585-24595.
[37]NCCN.NCCN Guidelines for Patients:Lung Cancer[EB/OL].https://www.nccn.org/patients/guidelines/lung-nsclc,2018-09-28.
[38]Zois CE,Giatromanolaki A,Kainulainen H,et al.Lung autophagic response following exposure of mice to whole body irradiation,with and without amifostine[J].Biochem Biophys Res Commun,2011,404(1):552-558.
[39]Gewirtz DA.The Challenge of Developing Autophagy Inhibition as a Therapeutic Strategy[J].Cancer Res,2016,76(19):5610-5614.
[40]Nazim UM,Moon JH,Lee JH,et al.Activation of autophagy flux by metformin downregulates cellular FLICE-like inhibitory protein and enhances TRAIL-induced apoptosis[J].Oncotarget,2016,7(17):23468-23481.
[41]Han W,Pan H,Chen Y,et al.EGFR tyrosine kinase inhibitors activate autophagy as a cytoprotective response in human lung cancer cells[J].PLo S One,2011,6(6):e18691.
[42]Chen T,Ren H,Thakur A,et al.Decreased Level of Klotho Contributes to Drug Resistance in Lung Cancer Cells:Involving in Klotho-Mediated Cell Autophagy[J].DNA Cell Biol,2016,35(12):751-757.
[43]Yu XS,Du J,Fan YJ,et al.Activation of endoplasmic reticulum stress promotes autophagy and apoptosis and reverses chemoresistance of human small cell lung cancer cells by inhibiting the PI3K/AKT/m TOR signaling pathway[J].Oncotarget,2016,7(47):76827-76839.
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