Inhibition of pyruvate kinase M2 by reactive oxygen species contributes to cellular antioxidant responses.

Published

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.

Full Text

Duke Authors

Cited Authors

  • 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

Published Date

  • December 2011

Published In

Volume / Issue

  • 334 / 6060

Start / End Page

  • 1278 - 1283

PubMed ID

  • 22052977

Pubmed Central ID

  • 22052977

Electronic International Standard Serial Number (EISSN)

  • 1095-9203

International Standard Serial Number (ISSN)

  • 0036-8075

Digital Object Identifier (DOI)

  • 10.1126/science.1211485

Language

  • eng