Autophagy is an ancient catabolic process used by cells to clear excess or dysfunctional organelles and large subcellular structures and thus performs an important housekeeping role for the cell. Autophagy is acutely sensitive to nutrient availability and is upregulated at a transcriptional and posttranslational level in response to nutrient deprivation. This serves to promote turnover of cellular content and recycling of nutrients for continued growth and survival. While important for most normal tissues, tumor cells appear to be particularly dependent on autophagy for survival under ischemic or therapeutic stress, and in response to loss of matrix attachment; autophagy is upregulated markedly in cancers as they progress to malignancy. Ras-driven tumors appear to be particularly dependent on autophagy and thus inhibition of autophagy is being pursued as a productive clinical approach for such cancers. However, this enthusiasm needs to be offset against possible negative effects of autophagy inhibition on normal tissue function and on limiting antitumor immune responses. In addressing all of these topics, we focus in on understanding how autophagy is induced by nutrient stress, its role in recycling metabolites for growing tumors, how selective forms of autophagy, such as mitophagy and ribophagy contribute specifically to tumorigenesis, how autophagy in the tumor microenvironment and throughout the animal affects access of the tumor to nutrients, and finally how different oncogenic pathways may determine which tumors respond to autophagy inhibition and which ones will not.

中文翻译：

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自噬和癌细胞代谢。

自噬是一种古老的分解代谢过程，细胞用来清除多余或功能失调的细胞器和大型亚细胞结构，从而对细胞发挥重要的管家作用。自噬对营养物质的可用性非常敏感，并且在转录和翻译后水平上上调以响应营养物质的缺乏。这有助于促进细胞内容物的周转和营养物质的循环利用，以实现持续生长和生存。虽然对大多数正常组织很重要，但肿瘤细胞似乎特别依赖自噬来在缺血或治疗应激下生存，并响应基质附着的丧失。当癌症进展为恶性肿瘤时，自噬在癌症中显着上调。Ras 驱动的肿瘤似乎特别依赖于自噬，因此抑制自噬正在被视为治疗此类癌症的有效临床方法。然而，这种热情需要抵消自噬抑制对正常组织功能和限制抗肿瘤免疫反应可能产生的负面影响。在讨论所有这些主题时，我们重点了解营养应激如何诱导自噬、其在循环代谢物以促进肿瘤生长中的作用、选择性形式的自噬（例如线粒体自噬和核糖自噬）如何专门促进肿瘤发生、肿瘤中的自噬如何微环境和整个动物会影响肿瘤对营养物质的获取，最后不同的致癌途径如何决定哪些肿瘤对自噬抑制有反应，哪些肿瘤不会。