The Bidirectional Relationship Between Cancer Epigenetics and Metabolism

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 modifying enzymes. Reciprocally, altered expression or activity of epigenetic 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. Expected final online publication date for the Annual Review of Cancer Biology, Volume 5 is March 4, 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Epigenetic, Metabolic, and Immune Crosstalk in Germinal-Center-Derived B-Cell Lymphomas: Unveiling New Vulnerabilities for Rational Combination Therapies

“…Epigenetic and metabolic reprogramming are usually deeply linked in cancer cells. The influence of tumor-intrinsic oncogenic signaling and tumor microenvironmental factors on the availability of metabolites that are substrates or inhibitors of epigenetic enzymes is well described (Kinnaird et al, 2016;Izzo et al, 2021). In addition, altered expression or activity of chromatin-modifying enzymes can impact directly and indirectly on cellular metabolism.…”

Micro but mighty—Micronutrients in the epigenetic regulation of adaptive immune responses*

“…Recent studies highlighting the links between metabolisms (mainly metabolites and macronutrients) and the epigenome have been reviewed previously. [3][4][5][6][7] Here, we will focus on the role of micronutrients (vitamins and minerals) and how they regulate the epigenome, using the Ten-Eleven Translocation (TET) enzymes and their cofactors ascorbate (VC) and iron as examples. We will first discuss the general role of DNA methylation and demethylation in the B and T lymphocytes, followed by the role of VC and iron in adaptive immune responses.…”

Emerging Single-Cell Technological Approaches to Investigate Chromatin Dynamics and Centromere Regulation in Human Health and Disease

“…In addition to monogenic diseases, epigenetic mechanisms are significantly involved in multifactorial diseases such as neurodegenerative disorders [20], metabolic dysfunction [21] and cancer progression [22], although it is unclear the degree by which epigenetic alterations are the cause or the consequence of pathogenesis. For example, epigenetic variability between cancer cells that may arise in response to environmental stimuli may exacerbate cell-to-cell heterogeneity and contribute to cancer progression and resistance to therapy [23].…”