Epigenetics represents a bridge between molecular biology and biochemistry. From the physiological point of view, epigenetics allows key adaptations of cells to external circumstances, taking advantage of biochemical substrates. The availability of metabolites themselves can regulate epigenetic modifications of the genome. The term epigenetics, indeed, refers to a broad range of transient modifications of DNA basis that alters the gene activity, but not the sequence. The result is a rapid and less expensive regulation of gene expression. Several types of epigenetic processes have been identified, including methylation, acetylation, phosphorylation, ubiquitylation, and sumoylation. Another crucial epigenetic process is chromatin modification, which alters chromatin structure to impact gene expression. In fact, tightly folded chromatin tends to be not expressed, while more open chromatin is actively expressed. Since many epigenetic modifications consist of transferring chemical groups deriving from biochemical intermediates (e.g. -CH3 for methylation, -CH3CO for acetylation), cell metabolism is a key regulator of the process.

Metabolism in tumor cells is altered, mainly to supply the increased energy demand deriving from the high proliferation rate. Indeed, metabolic reprogramming of cancer cells is a well-defined cancer hallmark, largely consisting of improving glycolysis and lactate production rather than glucose metabolization in mitochondria. As a result of oncogenes activation, cancer metabolism is modified during carcinogenesis, shifting toward aerobic glycolysis in a process known as the “Warburg effect”.

Thus, the current aims of this Research Topic are to gather articles focused on metabolic rewiring responsible for epigenetic modifications in cancer cells in order to:

• elucidate consequences of metabolic modifications in tumor other than the energetic one

• dissect epigenetic outcomes of therapies targeting metabolism

• define how the biunivocal relation between epigenetics and metabolism is altered in cancer cells

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Epigenetics and Metabolism: A Closed Liaison in Tumor Cells