How DNA methylation affects the Warburg effect

Int J Biol Sci. 2020 Apr 27;16(12):2029-2041. doi: 10.7150/ijbs.45420. eCollection 2020.

Abstract

Significant enhancement of the glycolysis pathway is a major feature of tumor cells, even in the presence of abundant oxygen; this enhancement is known as the Warburg effect, and also called aerobic glycolysis. The Warburg effect was discovered nearly a hundred years ago, but its specific mechanism remains difficult to explain. DNA methylation is considered to be a potential trigger for the Warburg effect, as the two processes have many overlapping links during tumorigenesis. Based on a widely recognized potential mechanism of the Warburg effect, we here summarized the relationship between DNA methylation and the Warburg effect with regard to cellular energy metabolism factors, such as glycolysis related enzymes, mitochondrial function, glycolysis bypass pathways, the tumor oxygen sensing pathway and abnormal methylation conditions. We believe that clarifying the relationship between these different mechanisms may further help us understand how DNA methylation works on tumorigenesis and provide new opportunities for cancer therapy.

Keywords: DNA methylation; aerobic glycolysis; mitochondria; reactive oxygen species; the Warburg effect.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • DNA Methylation / physiology*
  • DNA, Mitochondrial / genetics
  • Humans
  • Mitochondria / metabolism
  • Neoplasms / metabolism*
  • Warburg Effect, Oncologic*

Substances

  • DNA, Mitochondrial