Mason Emily F, Rathmell Jeffrey C
Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA.
Biochim Biophys Acta. 2011 Apr;1813(4):645-54. doi: 10.1016/j.bbamcr.2010.08.011. Epub 2010 Sep 8.
Growth factor-stimulated or cancerous cells require sufficient nutrients to meet the metabolic demands of cell growth and division. If nutrients are insufficient, metabolic checkpoints are triggered that lead to cell cycle arrest and the activation of the intrinsic apoptotic cascade through a process dependent on the Bcl-2 family of proteins. Given the connections between metabolism and apoptosis, the notion of targeting metabolism to induce cell death in cancer cells has recently garnered much attention. However, the signaling pathways by which metabolic stresses induce apoptosis have not as of yet been fully elucidated. Thus, the best approach to this promising therapeutic avenue remains unclear. This review will discuss the intricate links between metabolism, growth, and intrinsic apoptosis and will consider ways in which manipulation of metabolism might be exploited to promote apoptotic cell death in cancer cells. This article is part of a Special Issue entitled Mitochondria: the deadly organelle.
生长因子刺激的细胞或癌细胞需要足够的营养物质来满足细胞生长和分裂的代谢需求。如果营养物质不足,就会触发代谢检查点,导致细胞周期停滞,并通过一个依赖于Bcl-2蛋白家族的过程激活内源性凋亡级联反应。鉴于代谢与凋亡之间的联系,靶向代谢以诱导癌细胞死亡的概念最近备受关注。然而,代谢应激诱导凋亡的信号通路尚未完全阐明。因此,这条有前景的治疗途径的最佳方法仍不明确。本综述将讨论代谢、生长和内源性凋亡之间的复杂联系,并将探讨操纵代谢以促进癌细胞凋亡性细胞死亡的方法。本文是名为“线粒体:致命细胞器”的特刊的一部分。