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Science 324 (5930): 1029-1033

Copyright © 2009 by the American Association for the Advancement of Science

Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation

Matthew G. Vander Heiden,1,2 Lewis C. Cantley,2,* Craig B. Thompson3,*

Abstract: In contrast to normal differentiated cells, which rely primarily on mitochondrial oxidative phosphorylation to generate the energy needed for cellular processes, most cancer cells instead rely on aerobic glycolysis, a phenomenon termed "the Warburg effect." Aerobic glycolysis is an inefficient way to generate adenosine 5'-triphosphate (ATP), however, and the advantage it confers to cancer cells has been unclear. Here we propose that the metabolism of cancer cells, and indeed all proliferating cells, is adapted to facilitate the uptake and incorporation of nutrients into the biomass (e.g., nucleotides, amino acids, and lipids) needed to produce a new cell. Supporting this idea are recent studies showing that (i) several signaling pathways implicated in cell proliferation also regulate metabolic pathways that incorporate nutrients into biomass; and that (ii) certain cancer-associated mutations enable cancer cells to acquire and metabolize nutrients in a manner conducive to proliferation rather than efficient ATP production. A better understanding of the mechanistic links between cellular metabolism and growth control may ultimately lead to better treatments for human cancer.

1 Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
2 Beth-Israel Deaconess Cancer Center and Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
3 Department of Cancer Biology, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA 19104, USA.

* To whom correspondence should be addressed: E-mail: lewis_cantley{at}hms.harvard.edu; craig{at}mail.med.upenn.edu


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A. Cagnetta, M. Cea, T. Calimeri, C. Acharya, M. Fulciniti, Y.-T. Tai, T. Hideshima, D. Chauhan, M. Y. Zhong, F. Patrone, et al. (2013)
Blood 122, 1243-1255
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