Interplay between epigenetics and metabolism in oncogenesis: mechanisms and therapeutic approaches

Abstract

Epigenetic and metabolic alterations in cancer cells are highly intertwined. Oncogene-driven metabolic rewiring modifies the epigenetic landscape via modulating the activities of DNA and histone modification enzymes at the metabolite level. Conversely, epigenetic mechanisms regulate the expression of metabolic genes, thereby altering the metabolome. Epigenetic-metabolomic interplay has a critical role in tumourigenesis by coordinately sustaining cell proliferation, metastasis and pluripotency. Understanding the link between epigenetics and metabolism could unravel novel molecular targets, whose intervention may lead to improvements in cancer treatment. In this review, we summarized the recent discoveries linking epigenetics and metabolism and their underlying roles in tumorigenesis; and highlighted the promising molecular targets, with an update on the development of small molecule or biologic inhibitors against these abnormalities in cancer.

Figure 1

Crosstalks between epigenetics and metabolism in cancer development.

Figure 2

Effect of the tumor metabolome on the epigenetic processes such as histone acetylation, DNA methylation, DNA/histone demethylation, N-linked glycosylation in human cancers. An altered epigenetic regulation in turn contributes to deregulation of gene expression.

Figure 3

Effect of DNA hypermethylation (5mC), histone deacetylation (-Ac) and microRNA (miRs) on the expression of metabolic enzymes involved in glycolysis and glutaminolysis in cancer.