Cancer cell metabolism connects epigenetic modifications to transcriptional regulation.
Cancer cell metabolism connects epigenetic modifications to transcriptional regulation.
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DOI：
10.1111/febs.16032
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发表时间：
2022-03
期刊：
影响因子：
--
通讯作者：
Morrison AJ
中科院分区：
文献类型：
--
作者：
Morrison AJ
细胞功能与营养环境的适应是生存所必需的。不适应可能导致细胞死亡和/或疾病。事实上，能量代谢的改变是许多疾病的主要致病因素，包括癌症、心血管疾病和糖尿病。特别是，癌细胞的一个主要特征是代谢的改变，即使在营养有限的情况下也能促进生存和增殖。有趣的是，最近的研究表明，代谢途径产生直接影响基因组表观遗传修饰的中间代谢物。新出现的证据表明，癌细胞中的代谢过程促进恶性生长，部分是通过对增殖和适应性生存重要的基因表达程序的表观遗传调控。本文将对肿瘤细胞代谢、表观遗传修饰和转录调控之间的关系进行综述。具体来说，适应性细胞代谢的需要及其在癌细胞中的调节将被介绍。对代谢物生产和表观遗传修饰这一新兴领域的最新知识也进行了综述。DNA（去）甲基化的改变，组蛋白修饰，如（去）甲基化和（去）酰化，以及染色质重塑，将在癌细胞代谢的背景下讨论。最后，总结了这些表观遗传改变对癌细胞表型的影响。总的来说，这些研究揭示了癌细胞的代谢和表观遗传途径是密切相关的，代表了多种治疗靶向恶性生长的独特特征的机会。癌细胞的代谢促进恶性生长，部分是通过表观遗传调控对增殖和适应性生存很重要的基因表达程序。具体来说，细胞外代谢物提供了促进癌细胞生长的代谢途径。这些代谢途径也产生组蛋白修饰所需的中间代谢物，组蛋白修饰反过来调节细胞生长途径中基因的转录。
Adaptation of cellular function with the nutrient environment is essential for survival. Failure to adapt can lead to cell death and/or disease. Indeed, energy metabolism alterations are a major contributing factor for many pathologies, including cancer, cardiovascular disease, and diabetes. In particular, a primary characteristic of cancer cells is altered metabolism that promotes survival and proliferation even in the presence of limited nutrients. Interestingly, recent studies demonstrate that metabolic pathways produce intermediary metabolites that directly influence epigenetic modifications in the genome. Emerging evidence demonstrates that metabolic processes in cancer cells fuel malignant growth, in part, through epigenetic regulation of gene expression programs important for proliferation and adaptive survival. In this review, recent progress towards understanding the relationship of cancer cell metabolism, epigenetic modification, and transcriptional regulation will be discussed. Specifically, the need for adaptive cell metabolism and its modulation in cancer cells will be introduced. Current knowledge on the emerging field of metabolite production and epigenetic modification will also be reviewed. Alterations of DNA (de)methylation, histone modifications, such as (de)methylation and (de)acylation, as well as chromatin remodeling, will be discussed in the context of cancer cell metabolism. Finally, how these epigenetic alterations contribute to cancer cell phenotypes will summarized. Collectively, these studies reveal that both metabolic and epigenetic pathways in cancer cells are closely linked, representing multiple opportunities to therapeutically target the unique features of malignant growth. Cancer cell metabolism fuels malignant growth, in part, through epigenetic regulation of gene expression programs important for proliferation and adaptive survival. Specifically, extracellular metabolites feed metabolic pathways that promote cancer cell growth. These metabolic pathways also produce intermediary metabolites required for histone modifications, which in turn regulates transcription of genes in cell growth pathways.
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