Department of Biology, Stanford University, Stanford, CA, USA.
FEBS J. 2022 Mar;289(5):1302-1314. doi: 10.1111/febs.16032. Epub 2021 Jun 11.
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 toward 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 be 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.
细胞功能与营养环境的适应对于生存至关重要。如果不能适应，就会导致细胞死亡和/或疾病。事实上，能量代谢的改变是许多病理学的一个主要因素，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改变，即使在有限的营养物质存在的情况下，也能促进存活和增殖。有趣的是，最近的研究表明，代谢途径产生的中间代谢产物直接影响基因组中的表观遗传修饰。新出现的证据表明，癌细胞的代谢过程通过对增殖和适应性存活至关重要的基因表达程序的表观遗传调控，在一定程度上推动了恶性生长。在这篇综述中，将讨论近年来人们对癌细胞代谢、表观遗传修饰和转录调控之间关系的理解所取得的进展。具体来说，将介绍癌细胞代谢适应性及其在癌细胞中的调节的必要性。还将回顾代谢物产生和表观遗传修饰这一新兴领域的现有知识。将在癌细胞代谢的背景下讨论 DNA（去）甲基化、组蛋白修饰（如去甲基化和去乙酰化）以及染色质重塑的改变。最后，将总结这些表观遗传改变如何导致癌细胞表型。总的来说，这些研究表明，癌细胞中的代谢和表观遗传途径密切相关，为针对恶性生长的独特特征进行治疗提供了多种机会。
