Role of autophagy in cancer prevention.
Role of autophagy in cancer prevention.
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DOI：
10.1158/1940-6207.capr-10-0387
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发表时间：
2011-07
期刊：
影响因子：
--
通讯作者：
White E
中科院分区：
文献类型：
--
作者：
Chen HY;White E
巨自噬(以下简称自噬)是细胞降解溶酶体中细胞内成分的分解代谢过程。自噬提供的这种细胞垃圾处理和细胞内循环通过消除多余或受损的蛋白质和细胞器以及入侵的微生物来维持细胞动态平衡，或者在应激状态下为能量生成和生物合成提供底物。因此，自噬促进细胞和动物的健康，对于细胞功能的发育、分化和维持以及宿主对病原体的防御都是至关重要的。放松对自噬的管制与各种疾病的易感性有关，包括退行性疾病、代谢综合征、衰老、传染病和癌症。自噬活动在疾病的发展和进展中是一个关键因素，这些疾病与癌症风险增加以及癌症的不同阶段有关。鉴于癌症是一个复杂的过程，自噬以多种方式发挥其作用，自噬在肿瘤发生中的作用取决于背景。作为一种细胞保护的生存途径，自噬可以防止慢性组织损伤和细胞死亡，这些损伤和细胞死亡可能导致癌症的发生和发展。因此，刺激或恢复自噬可能会预防癌症。相比之下，一旦癌症发生，癌细胞可能会利用自噬来增强适应能力，以便在代谢改变的情况下和在充满敌意的肿瘤微环境中生存。在这种情况下，抑制自噬将成为治疗已确定癌症的一种策略。
Macroautophagy (autophagy hereafter) is a catabolic process by which cells degrade intracellular components in lysosomes. This cellular garbage disposal and intracellular recycling provided by autophagy serves to maintain cellular homeostasis by eliminating superfluous or damaged proteins and organelles, and invading microbes, or to provide substrates for energy generation and biosynthesis in stress. Thus, autophagy promotes the health of cells and animals and is critical for development, differentiation and maintenance of cell function and for the host defense against pathogens. Deregulation of autophagy is linked to susceptibility to various disorders including degenerative diseases, metabolic syndrome, aging, infectious diseases and cancer. Autophagic activity emerges as a critical factor in development and progression of diseases that are associated with increased cancer risk as well as in different stages of cancer. Given that cancer is a complex process and autophagy exerts its effect in multiple ways, role of autophagy in tumorigenesis is context-dependent. As a cytoprotective survival pathway, autophagy prevents chronic tissue damage and cell death that can lead to cancer initiation and progression. As such, stimulation or restoration of autophagy may prevent cancer. By contrast, once cancer occurs, cancer cells may utilize autophagy to enhance fitness to survive with altered metabolism and in the hostile tumor microenvironment. In this setting autophagy inhibition would instead become a strategy for therapy of established cancers.