The Cancer Institute of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08903, USA.
Curr Opin Cell Biol. 2010 Apr;22(2):212-7. doi: 10.1016/j.ceb.2009.12.008. Epub 2010 Jan 6.
Autophagy is a crucial component of the cellular stress adaptation response that maintains mammalian homeostasis. Autophagy protects against neurodegenerative and inflammatory conditions, aging, and cancer. This is accomplished by the degradation and intracellular recycling of cellular components to maintain energy metabolism and by damage mitigation through the elimination of damaged proteins and organelles. How autophagy modulates oncogenesis is gradually emerging. Tumor cells induce autophagy in response to metabolic stress to promote survival, suggesting deployment of therapeutic strategies to block autophagy for cancer therapy. By contrast, defects in autophagy lead to cell death, chronic inflammation, and genetic instability. Thus, stimulating autophagy may be a powerful approach for chemoprevention. Analogous to infection or toxins that create persistent tissue damage and chronic inflammation that increases the incidence of cancer, defective autophagy represents a cell-intrinsic mechanism to create the damaging, inflammatory environment that predisposes to cancer. Thus, cellular damage mitigation through autophagy is a novel mechanism of tumor suppression.
自噬是细胞应激适应反应的一个关键组成部分，它维持着哺乳动物的内稳态。自噬可以预防神经退行性和炎症性疾病、衰老和癌症。这是通过降解和细胞内再循环细胞成分来维持能量代谢，以及通过消除受损蛋白质和细胞器来减轻损伤来实现的。自噬如何调节肿瘤发生正在逐渐显现。肿瘤细胞在代谢应激时诱导自噬以促进生存，这表明可以部署治疗策略来阻断自噬以进行癌症治疗。相比之下，自噬缺陷会导致细胞死亡、慢性炎症和遗传不稳定性。因此，刺激自噬可能是化学预防的一种有效方法。类似于感染或毒素会造成持续的组织损伤和慢性炎症，从而增加癌症的发病率，自噬缺陷代表了一种内在的细胞机制，可以创造出易患癌症的破坏性、炎症性环境。因此，通过自噬减轻细胞损伤是一种新的肿瘤抑制机制。
