Understanding emerging bioactive metabolites with putative roles in cancer biology

Abstract

Dysregulated metabolism in cancers is, by now, well established. Although metabolic adaptations provide cancers with the ability to synthesize the precursors required for rapid biosynthesis, some metabolites have direct functional, or bioactive, effects in human cells. Here we summarize recently identified metabolites that have bioactive roles either as post-translational modifications (PTMs) on proteins or in, yet unknown ways. We propose that these metabolites could play a bioactive role in promoting or inhibiting cancer cell phenotypes in a manner that is mostly unexplored. To study these potentially important bioactive roles, we discuss several novel metabolomic and proteomic approaches aimed at defining novel PTMs and metabolite-protein interactions. Understanding metabolite PTMs and protein interactors of bioactive metabolites may provide entirely new therapeutic targets for cancer.

The Knowns and Unknowns in Protein–Metabolite Interactions

“…PMIs play a key role in regulating protein functions and directing the orchestra of cellular processes [ 4 , 5 , 6 ]. The interactions between proteins and metabolites form a highly dynamic adaptive molecular structure that functions harmoniously in healthy cells and tissues and is distorted in pathologies [ 7 ].…”