The Role of Autophagy in Cancer
The Role of Autophagy in Cancer
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DOI：
10.1146/annurev-cancerbio-041816-122338
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发表时间：
2017-01-01
期刊：
影响因子：
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通讯作者：
Kimmelman, Alec C.
中科院分区：
文献类型：
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作者：
Santana-Codina, Naiara;Mancias, Joseph D.;Kimmelman, Alec C.
自噬是一个高度保守和受调控的过程，以蛋白质和受损细胞器为目标进行溶酶体降解，以维持细胞代谢、基因组完整性和细胞存活。自噬在癌症中的作用是动态的，部分取决于肿瘤类型和阶段。尽管自噬限制正常组织中肿瘤的发生，但一些肿瘤依赖自噬来促进和维持肿瘤。基因工程小鼠模型的研究支持了这样的观点：自噬可以通过调节 DNA 损伤和氧化应激来抑制肿瘤的发生。在已形成的肿瘤中，自噬也可能是肿瘤维持所必需的，使肿瘤能够在环境压力下生存并为细胞代谢提供中间体。自噬也可以响应化疗而被诱导，作为一种耐药机制。因此，靶向自噬是一种有吸引力的癌症治疗选择，目前正在临床试验中进行验证。
Autophagy is a highly conserved and regulated process that targets proteins and damaged organelles for lysosomal degradation to maintain cell metabolism, genomic integrity, and cell survival. The role of autophagy in cancer is dynamic and depends, in part, on tumor type and stage. Although autophagy constrains tumor initiation in normal tissue, some tumors rely on autophagy for tumor promotion and maintenance. Studies in genetically engineered mouse models support the idea that autophagy can constrain tumor initiation by regulating DNA damage and oxidative stress. In established tumors, autophagy can also be required for tumor maintenance, allowing tumors to survive environmental stress and providing intermediates for cell metabolism. Autophagy can also be induced in response to chemotherapeutics, acting as a drug-resistance mechanism. Therefore, targeting autophagy is an attractive cancer therapeutic option currently undergoing validation in clinical trials.