Epigenetics is increasingly recognized to play an important role in
tumorigenesis. The epigenome encompasses a multitude of elements that regulate gene
expression, including DNA methylation, histone modification, microRNA, and more
recently, non-coding RNA. Aberrant regulation of the epigenome has been implicated
in altered gene expression and function, which contribute to cancer development and
progression via the promotion of cellular transformation, metastatic spread, and drug
resistance. Emerging evidence indicates that the activities of key epigenetic regulators
including DNA methyltransferases and histone modification enzymes are sensitive to
cellular metabolism. The efficiency of these metabolic enzymes depends on the
availability of substrates and/or co-factors that can be profoundly altered in cancer.
Mutations in metabolic enzymes in cancer also generate oncometabolites that can lead
to the dysfunction of DNA and histone demethylases. Conversely, through mediating
aberrant expression of genes that are involved in cellular metabolism, epigenetic
mechanisms could contribute to metabolic rewiring in cancer to confer a growth
advantage to cancer cells. Understanding this cross-talk between epigenetics and cancer
cell metabolism may unravel novel therapeutic opportunities. In this chapter, we will
review recent discoveries linking epigenetics and cancer cell metabolism, their
implications in oncogenesis, and highlight potential approaches to target these cancerspecific
abnormities therapeutically.
Keywords: Acetyl-coenzyme A, Cancer, Cancer metabolism, DNA methylation,
Epigenetics, Fumarate hydratase, Gene expression, Glutaminolysis, Glycolysis,
Histone acetylation, Histone demethylase, Histone methylation, Isocitrate
dehydrogenase, MicroRNA, Mitochondrial succinate dehydrogenase, Non-coding
RNA, S-adenosylmethionine, TET methyl-cytosine dioxygenase, Tricarboxylic
acid cycle, Warburg hypothesis.
