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代谢与表观遗传学:癌细胞利用的一种联系

Metabolism and epigenetics: a link cancer cells exploit.

作者信息

Carrer Alessandro, Wellen Kathryn E

机构信息

Department of Cancer Biology, Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Department of Cancer Biology, Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

出版信息

Curr Opin Biotechnol. 2015 Aug;34:23-9. doi: 10.1016/j.copbio.2014.11.012. Epub 2014 Nov 29.

Abstract

Both cellular nutrient metabolism and chromatin organization are remodeled in cancer cells, and these alterations play key roles in tumor development and growth. Many chromatin modifying-enzymes utilize metabolic intermediates as cofactors or substrates, and recent studies have demonstrated that the epigenome is sensitive to cellular metabolism. The contribution of metabolic alterations to epigenetic deregulation in cancer cells is just beginning to emerge, as are the roles of the metabolism-epigenetics link in tumorigenesis. Here we review the roles of acetyl-CoA and S-adenosylmethionine (SAM), donor substrates for acetylation and methylation reactions, respectively, in regulating chromatin modifications in response to nutrient metabolism. We further discuss how oncogenic signaling, cell metabolism, and histone modifications are interconnected and how their relationship might impact tumor growth.

摘要

癌细胞中的细胞营养代谢和染色质组织都会发生重塑,这些改变在肿瘤发展和生长中起关键作用。许多染色质修饰酶利用代谢中间产物作为辅因子或底物,最近的研究表明表观基因组对细胞代谢敏感。代谢改变对癌细胞表观遗传失调的影响刚刚开始显现,代谢与表观遗传学联系在肿瘤发生中的作用也是如此。在这里,我们综述了乙酰辅酶A和S-腺苷甲硫氨酸(SAM)分别作为乙酰化和甲基化反应的供体底物,在响应营养代谢调节染色质修饰中的作用。我们进一步讨论致癌信号、细胞代谢和组蛋白修饰是如何相互关联的,以及它们之间的关系可能如何影响肿瘤生长。

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