柳叶刀肿瘤特刊6.docx

AutophagyMediates Both TumorCell Survival andDeath自我吞噬能够接到肿瘤细胞的生存和死亡Autophagy represents an important cellphysiologic responsethat, like apoptosis, normally operates at low, basal levels in cellsbut can be strongly induced in certain states of cellular stress,the most obvious of which is nutrient de?ciency (Levine andKroemer, 2008; Mizushima, 2007). The autophagic programenables cells to break down cellular organelles, such as ribosomes and mitochondria, allowing the resulting catabolites tobe recycled and thus used for biosynthesis and energy metabolism. As part of this program, intracellular vesicles termed autophagosomes envelope intracellular organelles and then fusewithlysosomes wherein degradation occurs. In this fashion, low-molecular-weight metabolites are generated that supportsurvival in the stressed, nutrient-limited environments experienced by many cancer cells. Like apoptosis, the autophagy machinery has both regulatoryand effector components (Levine and Kroemer, 2008; Mizushima, 2007). Among the latter are proteins that mediate autophagosome formation and delivery to lysosomes. Of note, recentresearch has revealed intersections between the regulatorycircuits governing autophagy, apoptosis, and cellular homeostasis. For example, the signaling pathway involving the PI3kinase, AKT, and mTOR kinases, which is stimulated by survivalsignals to block apoptosis, similarly inhibits autophagy; whensurvival signals are insuf?cient, the PI3K signaling pathway isdownregulated, with the result that autophagy and/or apoptosismay be induced (Levine and Kroemer, 2008; Sinha and Levine,2008; Mathew et al., 2007).自我吞噬如同细胞凋亡一样是细胞重要的生理功能，通常，自我吞噬只在较低的、基础的水平出现，但是在一些重要的细胞阶段却可以被强力诱导上调，其中营养不良就是一个典型的例子。自我吞噬能够促使细胞分解一些细胞器，这些细胞器包括：核糖体、线粒体。分解这些细胞器所得的一些代谢产物能够用来进行当做生物合成和能量代谢的原料。在细胞内，有一些叫做吞噬体的物质能够包绕着细胞器，然后和溶酶体融合，随后，细胞器就会被降解。就这样，就会产生一些低分子量的物质，这些物质在肿瘤患者严重营养缺乏的情况下可以用来提供能量。和细胞凋亡一样，细胞的自我吞噬也有调控因子和效应元件。效应元件常常是一些蛋白质，他们能够接到自我吞噬的形成，并且将吞噬体运输到溶酶体当中。目前，一个非常有名气的研究已经证实了在调控细胞自我吞噬、凋亡和内平衡的信号转导中有一定的交集。比如