Tumour Cell Death Laboratory, Beatson Institute for Cancer Research, Garscube Estate, Glasgow, UK.
J Cell Sci. 2012 May 15;125(Pt 10):2349-58. doi: 10.1242/jcs.093708. Epub 2012 May 28.
Autophagy is an evolutionarily conserved catabolic pathway that has multiple roles in carcinogenesis and cancer therapy. It can inhibit the initiation of tumorigenesis through limiting cytoplasmic damage, genomic instability and inflammation, and the loss of certain autophagy genes can lead to cancer. Conversely, autophagy can also assist cells in dealing with stressful metabolic environments, thereby promoting cancer cell survival. In fact, some cancers rely on autophagy to survive and progress. Furthermore, tumour cells can exploit autophagy to cope with the cytotoxicity of certain anticancer drugs. By contrast, it appears that certain therapeutics require autophagy for the effective killing of cancer cells. Despite these dichotomies, it is clear that autophagy has an important, if complex, role in cancer. This is further exemplified by the fact that autophagy is connected with major cancer networks, including those driven by p53, mammalian target of rapamycin (mTOR), RAS and glutamine metabolism. In this Commentary, we highlight recent advances in our understanding of the role that autophagy has in cancer and discuss current strategies for targeting autophagy for therapeutic gain.
自噬是一种进化上保守的分解代谢途径，在致癌作用和癌症治疗中有多种作用。它可以通过限制细胞质损伤、基因组不稳定性和炎症来抑制肿瘤发生的起始，而某些自噬基因的缺失会导致癌症。相反，自噬也可以帮助细胞应对应激代谢环境，从而促进癌细胞的存活。事实上，一些癌症依赖自噬来存活和发展。此外，肿瘤细胞可以利用自噬来应对某些抗癌药物的细胞毒性。相比之下，某些治疗方法似乎需要自噬才能有效地杀死癌细胞。尽管存在这些二分法，但自噬在癌症中具有重要作用（即使作用复杂），这一点是明确的。自噬与包括 p53、雷帕霉素靶蛋白（mTOR）、RAS 和谷氨酰胺代谢驱动的主要癌症网络有关，这进一步证明了这一点。在这篇评论中，我们强调了我们对自噬在癌症中的作用的理解的最新进展，并讨论了目前针对自噬以获得治疗效果的策略。
