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


How DNA methylation affects the Warburg effect

Xingxin Zhu1,2,3,4, Zefeng Xuan1,2,3,4, Jun Chen1,2,3,4, Zequn Li1,2,3,4, Shusen Zheng1,2,3,4,✉, Penghong Song1,2,3,4,✉

1. Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University
2. NHC Key Laboratory of Combined Multi-organ Transplantation
3. Key Laboratory of the diagnosis and treatment of organ Transplantation, Research Unit of Collaborative Diagnosis and Treatment For Hepatobiliary and Pancreatic Cancer, Chinese Academy of Medical Sciences (2019RU019)
4. Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou 310003, China

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Zhu X, Xuan Z, Chen J, Li Z, Zheng S, Song P. How DNA methylation affects the Warburg effect. Int J Biol Sci 2020; 16(12):2029-2041. doi:10.7150/ijbs.45420. Available from

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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: the Warburg effect, DNA methylation, aerobic glycolysis, mitochondria, reactive oxygen species