Cell Death Regulation Group, IDIBELL (Bellvitge Biomedical Research Institute), Gran Via de L'Hospitalet 199, L'Hospitalet, Barcelona 08908 Spain.
Cell Death Dis. 2012 Jan 12;3(1):e248. doi: 10.1038/cddis.2011.123.
Cellular metabolism influences life and death decisions. An emerging theme in cancer biology is that metabolic regulation is intricately linked to cancer progression. In part, this is due to the fact that proliferation is tightly regulated by availability of nutrients. Mitogenic signals promote nutrient uptake and synthesis of DNA, RNA, proteins and lipids. Therefore, it seems straight-forward that oncogenes, that often promote proliferation, also promote metabolic changes. In this review we summarize our current understanding of how 'metabolic transformation' is linked to oncogenic transformation, and why inhibition of metabolism may prove a cancer's 'Achilles' heel'. On one hand, mutation of metabolic enzymes and metabolic stress sensors confers synthetic lethality with inhibitors of metabolism. On the other hand, hyperactivation of oncogenic pathways makes tumors more susceptible to metabolic inhibition. Conversely, an adequate nutrient supply and active metabolism regulates Bcl-2 family proteins and inhibits susceptibility to apoptosis. Here, we provide an overview of the metabolic pathways that represent anti-cancer targets and the cell death pathways engaged by metabolic inhibitors. Additionally, we will detail the similarities between metabolism of cancer cells and metabolism of proliferating cells.
细胞代谢影响生死决策。癌症生物学中的一个新兴主题是，代谢调控与癌症进展密切相关。部分原因是增殖受到营养物质可用性的严格调控。有丝分裂信号促进营养物质的摄取和 DNA、RNA、蛋白质和脂质的合成。因此，似乎很明显，经常促进增殖的癌基因也会促进代谢变化。在这篇综述中，我们总结了我们目前对“代谢转化”如何与致癌转化相关联的理解，以及为什么抑制代谢可能成为癌症的“阿喀琉斯之踵”。一方面，代谢酶和代谢应激传感器的突变赋予了代谢抑制剂的合成致死性。另一方面，致癌途径的过度激活使肿瘤更容易受到代谢抑制的影响。相反，充足的营养供应和活跃的代谢调节 Bcl-2 家族蛋白并抑制对细胞凋亡的敏感性。在这里，我们概述了代表抗癌靶点的代谢途径和代谢抑制剂所涉及的细胞死亡途径。此外，我们将详细描述癌细胞代谢和增殖细胞代谢之间的相似之处。
