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Targeting the interplay between metabolism and epigenetics in cancer

Montellier, Emiliea; Gaucher, Jonathanb

doi: 10.1097/CCO.0000000000000501
CANCER BIOLOGY: Edited by Pierre Hainaut

Purpose of review Metabolic perturbation is a hallmark of cancer favoring tumor progression. It is now demonstrated that cell metabolism has an impact on gene expression through epigenetic modifications. In this review, we expose recent evidences of metabolic-driven epigenetic perturbations in cancer and subsequent therapeutic opportunities.

Recent findings The intimate link between metabolism and epigenetics and its rewiring in carcinogenesis is a hot topic. Chromatin-modifying enzymes involved in the dynamics of methylation or acetylation require small metabolites as cofactors or substrates, thus orchestrating the integration between epigenetic and transcriptional states. Mutations in metabolic enzymes such as isocitrate dehydrogenase 1 and 2 cause the accumulation of metabolites that upset the balance of histone and DNA methylation, thus generating widespread deregulation of epigenetically controlled gene expression. Additionally, modifications of catalytic activity and subcellular localization of metabolic enzymes in cancer can impact on epigenetic modifications and gene expression programs to favor tumor progression.

Summary The interplay between metabolism and epigenetics and its molecular characterization in cancer cells identifies potential targets for the development of new therapies.

aInstitute for Advanced Biosciences, INSERM U1209 CNRS 5309 Université Grenoble Alpes

bHP2 laboratory, INSERM U1042 Université Grenoble Alpes, Grenoble, France

Correspondence to Emilie Montellier, PhD, Institute for Advanced Biosciences, Allée des Alpes, 38700 La Tronche, France. Tel: +33 4 76 54 95 76; e-mail: Emilie.montellier@univ-grenoble-alpes.fr

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