Codependency of Metabolism and Epigenetics Drives Cancer Progression: A Review.

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Accounts of Chemical Research Pub Date : 2020-02-28 Epub Date: 2020-02-26 DOI:10.1267/ahc.20002

Kenta Masui, Mio Harachi, Webster K Cavenee, Paul S Mischel, Noriyuki Shibata

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引用次数: 0

Abstract

Cancer is widely considered to be a set of genetic diseases that are currently classified by tissue and cell type of origin and, increasingly, by its molecular characteristics. This latter aspect is based primarily upon oncogene gains, tumor suppressor losses, and associated transcriptional profiles. However, cancers are also characterized by profound alterations in cellular metabolism and epigenetic landscape. It is particularly noteworthy that cancer-causing genomic defects not only activate cell cycle progression, but regulate the opportunistic uptake and utilization of nutrients, effectively enabling tumors to maximize growth and drug resistance in changing tissue and systemic microenvironments. Shifts in chromatin architecture are central to this dynamic behavior. Further, changes in nutrient uptake and utilization directly affect chromatin structure. In this review, we describe a set of recent discoveries of metabolic and epigenetic reprogramming in cancer, and especially focus on the genomically well-characterized brain tumor, glioblastoma. Further, we discuss a new mode of metabolic regulation driven by epigenetic mechanisms, that enables cancer cells to autonomously activate iron metabolism for their survival. Together, these underscore the integration of genetic mutations with metabolic reprogramming and epigenetic shifts in cancer, suggesting a new means to identifying patient subsets suitable for specific precision therapeutics.

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新陈代谢与表观遗传学的相互依存关系推动癌症进展：综述。

癌症被广泛认为是一系列遗传性疾病，目前是按照起源的组织和细胞类型进行分类，而且越来越多地按照其分子特征进行分类。后一方面主要基于癌基因的增殖、肿瘤抑制因子的缺失以及相关的转录特征。然而，癌症的另一个特征是细胞代谢和表观遗传结构的深刻改变。尤其值得注意的是，致癌基因组缺陷不仅会激活细胞周期的进展，还会调节营养物质的机会性摄取和利用，从而有效地使肿瘤在不断变化的组织和系统微环境中最大限度地生长和耐药。染色质结构的变化是这种动态行为的核心。此外，营养物质摄取和利用的变化会直接影响染色质结构。在这篇综述中，我们介绍了最近在癌症中发现的一系列代谢和表观遗传重编程现象，并特别关注了基因组学特征良好的脑肿瘤--胶质母细胞瘤。此外，我们还讨论了一种由表观遗传机制驱动的新的代谢调控模式，这种模式使癌细胞能够自主激活铁代谢，从而获得生存。这些共同强调了癌症中基因突变与代谢重编程和表观遗传学转变的结合，为确定适合特定精准疗法的患者亚群提出了一种新方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.