肿瘤细胞中染色质修饰与代谢的相互调控  

Interplay between chromatin modifications and metabolism in cancer

作　　者：向莹 熊洁[1] 李枫[1] XIANG Ying;XIONG Jie;LI Feng(School of Basic Medical Sciences,Wuhan University,Wuhan 430071,Hubei,China)

机构地区：[1]武汉大学基础医学院,武汉430071

出　　处：《肿瘤代谢与营养电子杂志》2019年第4期499-504,共6页Electronic Journal of Metabolism and Nutrition of Cancer

基　　金：国家自然科学基金(91859206);武汉大学医学腾飞计划(TFJC2018003)。

摘　　要：肿瘤细胞中表观遗传的改变可影响癌基因和抑癌基因的表达水平;此外,肿瘤细胞中伴有的葡萄糖消耗增加、氧化磷酸化减少以及大量乳酸生成等代谢重编程现象,为生物合成提供了更多的中间代谢产物,并重新平衡了肿瘤细胞的氧化还原状态。而表观遗传的改变和代谢重编程均是肿瘤细胞的重要标志。随着研究的不断深入,发现肿瘤细胞代谢和表观遗传(主要是染色质修饰)之间存在着重要的双向调节机制。代谢重编程可影响染色质修饰酶所需的辅助因子,产生的肿瘤代谢产物作为染色质修饰酶的激动剂或拮抗剂,影响染色质修饰;反之,染色质修饰可以直接调控代谢酶的表达,或者改变参与细胞代谢控制的级联信号转导来调节细胞代谢。因此,代谢与表观遗传通过相互调控影响着细胞增殖、转移和多能性,并在肿瘤发生、发展中发挥关键作用。在这篇综述中,我们总结了肿瘤细胞中染色质修饰和代谢相关的最新发现及相互调控机制,以期揭示其在肿瘤发生、发展中的潜在作用,为发展基于肿瘤表观遗传修饰和代谢的靶向治疗方案提供新策略。The expression levels of oncogenes and tumor suppressor genes are altered significantly by epigenetic changes in cancer cells.In addition,tumor cells are associated with metabolic reprogramming events such as increased glucose consumption,decreased oxidative phosphorylation,and large amounts of lactic acid production,providing more intermediate metabolites for biosynthesis and rebalancing the redox state of tumor cells.Both epigenetic and metabolic changes are distinct hallmarks of cancer.Along with the research,it now become evident that there is an important bidirectional regulatory mechanism between cancer metabolism and epigenetics(mainly refer to chromatin modifications).Metabolic reprogramming may affect the availability of cofactors required for normal function of epigenetic enzymes,and the oncometabolites probably act as agonists and/or antagonists of these enzymes,therefore affecting the epigenetic landscape.Moreover,chromatin modifications are able to directly regulate the expression of metabolic enzymes or change the signal transduction cascade involved in cell metabolism.Thus,epigenetic-metabolomic interplay plays a crucial role in tumorigenesis by sustaining cell proliferation,metastasis and pluripotency.Here,we summarized the mechanisms underlying mutual regulation of chromatin modifications and metabolism in cancer by reviewing the recent research progress,to explain their potential role in tumorigenesis,and provided new strategies for the development of therapies targeting epigenetic modifications and metabolism in cancer.

关 键 词：染色质修饰 代谢重编程 肿瘤 

分 类 号：R730.2[医药卫生—肿瘤]