Editors' ChoiceCancer

Cancer Cell Vulnerability

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Sci. Signal.  06 Dec 2011:
Vol. 4, Issue 202, pp. ec338
DOI: 10.1126/scisignal.4202ec338

Many cancer cells express an alternatively spliced form of the metabolic enzyme pyruvate kinase, pyruvate kinase M2 (PKM2). PKM2 is thought to help cancer cells use glucose efficiently to help in the production of molecules required for rapid cellular proliferation. Anastasiou et al. (see the Perspective by Hamanaka and Chandel) now report another advantage for cancer cells expressing PKM2. PKM2 is sensitive to oxidation by reactive oxygen species (ROS), which decreases its activity. Alterations in cancer cells and properties of their environment tend to increase ROS levels, causing toxicity. Inhibition of PKM2 appears to combat toxicity by promoting metabolic changes that help the cell to cope with the excess ROS. Thus, promoting sustained activation of PKM could offer a way to selectively target cancer cells.

D. Anastasiou, G. Poulogiannis, J. M. Asara, M. B. Boxer, J.-k. Jiang, M. Shen, G. Bellinger, A. T. Sasaki, J. W. Locasale, D. S. Auld, C. J. Thomas, M. G. Vander Heiden, L. C. Cantley, Inhibition of pyruvate kinase M2 by reactive oxygen species contributes to cellular antioxidant responses. Science 334, 1278–1283 (2011). [Abstract] [Full Text]

R. B. Hamanaka, N. S. Chandel, Warburg effect and redox balance. Science 334, 1219–1220 (2011). [Abstract] [Full Text]

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