自噬在肿瘤上皮-间充质转化以及侵袭转移中的作用
摘要
自噬和上皮-间充质转化(EMT)都参与了癌症进展。根据底物的降解途径不同,自噬可分为大自噬、小自噬、分子伴侣介导自噬,其均能使肿瘤细胞更加适应环境的压力,如饥饿、缺氧和药物影响等。EMT使肿瘤细胞失去上皮细胞的特性,获得间质细胞的特性,因而具有更强的侵袭迁移能力。研究表明:自噬对肿瘤细胞的侵袭转移起重要作用,这与其对EMT的作用密切相关。但不同的肿瘤细胞在不同的环境下所诱导的自噬对EMT的作用不同。本文对该领域目前的进展进行总结分析。
引文
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[34] KON M,KIFFIN R,KOGA H,et al.Chaperone-mediated autophagy is required for tumor growth[J].Sci Transl Med,2011,3(109):109-117.
[35] TANG J,ZHAN MN,YIN QQ,et al.Impaired p65 degradation by decreased chaperone-mediated autophagy activity facilitates epithelial-to-mesenchymal transition [J].Oncogenesis,2017,6(10):387-397.
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[2] OKU M,SAKAI Y.Three distinct types of microautophagy based on membrane dynamics and molecular machineries[J].Bioessays,2018,40(6):1-6.
[3] TEKIRDAG K,CUERVO AM.Chaperone-mediated autophagy and endosomal microautophagy:Joint by a chaperone[J].J Biol Chem,2018,293(15):5414-5424.
[4] ROSZEK K,GNIOT-SZULZYCKA J.Lysosomal membrane glycoprotein lamp2a-receptor for chaperone-mediated degradation of cytosolic proteins[J].Postepy Biochem,2005,51(1):88-94.
[5] SINGH M,YELLE N,VENUGOPAL C,et al.Emt:mechanisms and therapeutic implications[J].Pharmacol Ther,2018,182:80-94.
[6] FU J,QIN L,HE T,et al.The twist/mi2/nurd protein complex and its essential role in cancer metastasis[J].Cell Res,2011,21(2):275-289.
[7] ZHENG X,CARSTENS JL,KIM J,et al.Epithelial-to-mesenchymal transition is dispensable for metastasis but induces chemoresistance in pancreatic cancer[J].Nature,2015,527(7579):525-530.
[8] FISCHER KR,DURRANS A,LEE S,et al.Epithelial-to-mesenchymal transition is not required for lung metastasis but contributes to chemoresistance[J].Nature,2015,527(7579):472-476.
[9] PAL M,BHATTACHARYA S,KALYAN G,et al.Cadherin profiling for therapeutic interventions in epithelial mesenchymal transition (emt) and tumorigenesis[J].Exp Cell Res,2018,368(2):137-146.
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[12] ZHANG J,TIAN XJ,XING J.Signal transduction pathways of emt induced by tgf-β,shh,and wnt and their crosstalks[J].J Clin Med,2016,5(4):41-59.
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[23] PAN J,TAO YF,ZHOU Z,et al.An novel role of sphingosine kinase-1 (sphk1) in the invasion and metastasis of esophageal carcinoma[J].J Transl Med,2011,9(1):1-15.
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[34] KON M,KIFFIN R,KOGA H,et al.Chaperone-mediated autophagy is required for tumor growth[J].Sci Transl Med,2011,3(109):109-117.
[35] TANG J,ZHAN MN,YIN QQ,et al.Impaired p65 degradation by decreased chaperone-mediated autophagy activity facilitates epithelial-to-mesenchymal transition [J].Oncogenesis,2017,6(10):387-397.
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