文章：

癌症表观遗传学的代谢控制

Metabolic control of epigenetics in cancer

原文发布日期：2016-09-16

DOI: 10.1038/nrc.2016.82

类型: Review Article

开放获取: 否

要点：

1. The histone code is regulated by epigenetic 'readers', 'writers' and 'erasers'. This Review proposes adding to this paradigm the availability of the 'ink' needed to pen chromatin modifications, with the ink being metabolites that are substrates of chromatin-modifying enzymes (that is, for example, acetyl-CoA is the ink for acetyltransferases).
2. This Review puts forward a three-model framework by which metabolism can regulate the epigenome: inhibitor metabolite production; nutrient sensing and chromatin regulation; and localized metabolite production.
3. Metabolic and epigenetic changes are both common features found in all cancer types. Metabolic rewiring in cancer cells provides advantages not only through direct metabolic functions, but also by acting on the epigenetic landscape.
4. Cell signalling has long been known to affect nutrient uptake and use. However, metabolism also feeds back onto signalling pathways to play an active part in major cellular decisions, such as proliferation or differentiation. This reciprocal feedback between cell signalling and metabolism is manipulated in cancer cells to provide growth and survival advantages.
5. Improved understanding of the interplay between cell metabolism and the epigenome will be crucial in designing novel cancer therapeutic strategies.

要点翻译：

1. 组蛋白密码受表观遗传"阅读器"、"书写器"和"擦除器"的调控。本综述提出在此范式基础上增加书写染色质修饰所需"墨水"的可及性——这些墨水即作为染色质修饰酶底物的代谢物（例如，乙酰辅酶A是乙酰转移酶的墨水）。
2. 本综述提出了代谢调控表观基因组的三模式框架：抑制性代谢物产生；营养感知与染色质调控；以及局部代谢物产生。
3. 代谢改变与表观遗传改变是所有癌症类型中共同存在的特征。癌细胞的代谢重编程不仅通过直接代谢功能提供优势，还通过作用于表观遗传景观发挥作用。
4. 细胞信号传导影响营养物质的摄取和利用早已为人所知。然而，代谢也会反馈至信号通路，在细胞重大决策（如增殖或分化）中发挥积极作用。癌细胞通过操纵细胞信号传导与代谢之间的这种双向反馈来获得生长和生存优势。
5. 深化对细胞代谢与表观基因组相互作用的理解，对于设计新型癌症治疗策略至关重要。

英文摘要：

Alterations in the epigenome and metabolism both affect molecular rewiring in cancer cells and facilitate cancer development and progression. However, recent evidence suggests the existence of important bidirectional regulatory mechanisms between metabolic remodelling and the epigenome (specifically methylation and acetylation of histones) in cancer. Most chromatin-modifying enzymes require substrates or cofactors that are intermediates of cell metabolism. Such metabolites, and often the enzymes that produce them, can transfer into the nucleus, directly linking metabolism to nuclear transcription. We discuss how metabolic remodelling can contribute to tumour epigenetic alterations, thereby affecting cancer cell differentiation, proliferation and/or apoptosis, as well as therapeutic responses.

摘要翻译： 

表观基因组和代谢的改变都会影响癌细胞中的分子重编程，并促进癌症的发生和进展。然而，最近的证据表明，在癌症中，代谢重塑与表观基因组（特别是组蛋白的甲基化和乙酰化）之间存在重要的双向调控机制。大多数染色质修饰酶需要细胞代谢中间产物作为底物或辅因子。这些代谢物，以及产生它们的酶，通常可以进入细胞核，从而将代谢与核转录直接联系起来。我们讨论了代谢重塑如何促进肿瘤表观遗传改变，进而影响癌细胞的分化、增殖和/或凋亡，以及对治疗的反应。

原文链接：

Metabolic control of epigenetics in cancer