Inhibition of pyruvate kinase M2 by reactive oxygen species contributes to cellular antioxidant responses.
Journal Article (Journal Article)
Control of intracellular reactive oxygen species (ROS) concentrations is critical for cancer cell survival. We show that, in human lung cancer cells, acute increases in intracellular concentrations of ROS caused inhibition of the glycolytic enzyme pyruvate kinase M2 (PKM2) through oxidation of Cys(358). This inhibition of PKM2 is required to divert glucose flux into the pentose phosphate pathway and thereby generate sufficient reducing potential for detoxification of ROS. Lung cancer cells in which endogenous PKM2 was replaced with the Cys(358) to Ser(358) oxidation-resistant mutant exhibited increased sensitivity to oxidative stress and impaired tumor formation in a xenograft model. Besides promoting metabolic changes required for proliferation, the regulatory properties of PKM2 may confer an additional advantage to cancer cells by allowing them to withstand oxidative stress.
- Anastasiou, D; Poulogiannis, G; Asara, JM; Boxer, MB; Jiang, J-K; Shen, M; Bellinger, G; Sasaki, AT; Locasale, JW; Auld, DS; Thomas, CJ; Vander Heiden, MG; Cantley, LC
- December 2, 2011
Volume / Issue
- 334 / 6060
Start / End Page
- 1278 - 1283
Pubmed Central ID
Electronic International Standard Serial Number (EISSN)
Digital Object Identifier (DOI)
- United States