Tumour Cell Death Laboratory, Beatson Institute for Cancer Research, Glasgow, G61 1BD, UK.
Expert Rev Mol Med. 2009 Dec 2;11:e36. doi: 10.1017/S1462399409001306.
Autophagy is a catabolic membrane-trafficking process that leads to sequestration and degradation of intracellular material within lysosomes. It is executed at basal levels in every cell and promotes cellular homeostasis by regulating organelle and protein turnover. In response to various forms of cellular stress, however, the levels and cargoes of autophagy can be modulated. In nutrient-deprived states, for example, autophagy can be activated to degrade cargoes for cell-autonomous energy production to promote cell survival. In other contexts, in contrast, autophagy has been shown to contribute to cell death. Given these dual effects in regulating cell viability, it is no surprise that autophagy has implications in both the genesis and treatment of malignant disease. In this review, we provide a comprehensive appraisal of the way in which oncogenes and tumour suppressor genes regulate autophagy. In addition, we address the current evidence from human cancer and animal models that has aided our understanding of the role of autophagy in tumour progression. Finally, the potential for targeting autophagy therapeutically is discussed in light of the functions of autophagy at different stages of tumour progression and in normal tissues.
自噬是一种分解代谢的膜运输过程，导致溶酶体内细胞内物质的隔离和降解。它在每个细胞的基础水平上执行，并通过调节细胞器和蛋白质周转来促进细胞内稳态。然而，在响应各种形式的细胞应激时，自噬的水平和货物可以被调节。例如，在营养缺乏状态下，自噬可以被激活以降解货物，以进行细胞自主能量产生，从而促进细胞存活。在其他情况下，自噬已被证明有助于细胞死亡。鉴于自噬在调节细胞活力方面的双重作用，毫不奇怪，自噬在恶性疾病的发生和治疗中都有影响。在这篇综述中，我们全面评估了癌基因和肿瘤抑制基因调节自噬的方式。此外，我们还讨论了来自人类癌症和动物模型的当前证据，这些证据有助于我们理解自噬在肿瘤进展中的作用。最后，根据自噬在肿瘤进展的不同阶段和正常组织中的功能，讨论了靶向自噬治疗的潜力。
