Abstract
Metabolic and epigenetic reprogramming are characteristics of cancer cells that, in many cases, are linked. Oncogenic signaling, diet, and tumor microenvironment each influence the availability of metabolites that are substrates or inhibitors of epigenetic enzymes. Reciprocally, altered expression or activity of chromatin-modifying enzymes can exert direct and indirect effects on cellular metabolism. In this article, we discuss the bidirectional relationship between epigenetics and metabolism in cancer. First, we focus on epigenetic control of metabolism, highlighting evidence that alterations in histone modifications, chromatin remodeling, or the enhancer landscape can drive metabolic features that support growth and proliferation. We then discuss metabolic regulation of chromatin-modifying enzymes and roles in tumor growth and progression. Throughout, we highlight proposed therapeutic and dietary interventions that leverage metabolic-epigenetic cross talk and have the potential to improve cancer therapy.
Highlights
The development and progression of cancer involves the acquisition of several hallmark features, including altered metabolism (Hanahan & Weinberg 2011)
We discuss evidence that mutations in or overexpression of histone methyltransferases or demethylases mediates metabolic reprogramming in cancer cells, focusing on enhancer of zeste homolog 2 (EZH2), euchromatic histone lysine methyltransferase 2 (EHMT2), lysine methyltransferase 2D (KMT2D), and lysine-specific histone demethylase 1 (LSD1)
This is exemplified by aberrant expression of branched-chain amino acid transaminase 1 (BCAT1) (Gu et al 2019, Wang et al 2019), an enzyme that catalyzes the reversible interconversion of branched-chain amino acids (BCAAs) and branched-chain alphaketo acids (BCKAs), utilizing alpha-ketoglutarate and glutamate as the amino group acceptor or donor, respectively (Figure 2)
Summary
Annu. Rev. Cancer Biol. 2021.5:235-257. Downloaded from www.annualreviews.org Access provided by 3.86.84.87 on 11/08/21. See copyright for approved use. The Annual Review of Cancer Biology is online at cancerbio.annualreviews.org https://doi.org/10.1146/annurev-cancerbio-070820035832
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