细胞自噬与肿瘤发生的关系

Relationship Between Autophagy and Tumorigenesis

细胞自噬(autophagy)是将细胞内受损、变性或衰老的蛋白质以及细胞器运输到溶酶体进行消化降解的过程.正常生理情况下,细胞自噬利于细胞保持自稳状态;在发生应激时,细胞自噬防止有毒或致癌的损伤蛋白质和细胞器的累积,抑制细胞癌变;然而肿瘤一旦形成,细胞自噬为癌细胞提供更丰富的营养,促进肿瘤生长.因此,在肿瘤发生发展的过程中,细胞自噬的作用具有两面性.尽管大多数抑癌蛋白可以激活细胞自噬这一结论被广泛接受,但p53作为重要的抑癌蛋白,在细胞核和细胞浆不同的亚细胞定位中对细胞自噬有着截然相反的调控.对于细胞自噬和癌症发生之间关系亟待深入的研究,这将会有助于人类更好地认识并最终攻克癌症.本文将针对细胞自噬与肿瘤发生过程中主要的信号调节通路展开介绍.

Autophagy is a highly conserved catabolic process that degrades a bulk of misfolded or damaged proteins and organelles.In normal cells,autophagy functions primarily to maintain the cellular homeostasis and is responsible for the regulation of organelle turnover.In response to various cellular stresses,autophagy plays a crucial role in preventing the accumulation of damaged proteins and organelles which are toxic and carcinogenic.However,autophagy can promote tumor growth once the tumors are formed by supplying nutrition and energy to tumors.Thus autophagy exhibits the effects of a double-blade sword in cancers,where most tumor suppressors act as inducers of autophagy and oncogenes play inhibitory roles in autophagy.Yet an exceptional case has been reported-tumor suppressor p53 suppresses the induction of autophagy in the cytoplasm.In this review,we focus on the discussion about the relationship between autophagy and tumor development.