Serine, glycine and one‑carbon metabolism in cancer (Review).

Abstract

Serine/glycine biosynthesis and one-carbon metabolism are crucial in sustaining cancer cell survival and rapid proliferation, and of high clinical relevance. Excessive activation of serine/glycine biosynthesis drives tumorigenesis and provides a single carbon unit for one-carbon metabolism. One-carbon metabolism, which is a complex cyclic metabolic network based on the chemical reaction of folate compounds, provides the necessary proteins, nucleic acids, lipids and other biological macromolecules to support tumor growth. Moreover, one-carbon metabolism also maintains the redox homeostasis of the tumor microenvironment and provides substrates for the methylation reaction. The present study reviews the role of key enzymes with tumor-promoting functions and important intermediates that are physiologically relevant to tumorigenesis in serine/glycine/one-carbon metabolism pathways. The related regulatory mechanisms of action of the key enzymes and important intermediates in tumors are also discussed. It is hoped that investigations into these pathways will provide new translational opportunities for human cancer drug development, dietary interventions, and biomarker identification.