One-carbon metabolism: Biological players in epithelial ovarian cancer

Abstract

Metabolism is deeply involved in cell behavior and homeostasis maintenance, with metabolites acting as molecular intermediates to modulate cellular functions. In particular, one-carbon metabolism is a key biochemical pathway necessary to provide carbon units required for critical processes, including nucleotide biosynthesis, epigenetic methylation, and cell redox-status regulation. It is, therefore, not surprising that alterations in this pathway may acquire fundamental importance in cancer onset and progression. Two of the major actors in one-carbon metabolism, folate and choline, play a key role in the pathobiology of epithelial ovarian cancer (EOC), the deadliest gynecological malignancy. EOC is characterized by a cholinic phenotype sustained via increased activity of choline kinase alpha, and via membrane overexpression of the alpha isoform of the folate receptor (FRα), both of which are known to contribute to generating regulatory signals that support EOC cell aggressiveness and proliferation. Here, we describe in detail the main biological processes associated with one-carbon metabolism, and the current knowledge about its role in EOC. Moreover, since the cholinic phenotype and FRα overexpression are unique properties of tumor cells, but not of normal cells, they can be considered attractive targets for the development of therapeutic approaches.