Akt Stimulates Aerobic Glycolysis in Cancer Cells

Cancer Research - Tập 64 Số 11 - Trang 3892-3899 - 2004
Rebecca Elstrom1, Daniel E. Bauer1, Monica Buzzai1, Robyn Karnauskas2, Marian H. Harris1, David R. Plas1, Hongming Zhuang3, Ryan M. Cinalli1, Abass Alavi3, Charles M. Rudin4, Craig B. Thompson1
11Abramson Family Cancer Research Institute, Department of Cancer Biology, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania;
23Department of Medicine, University of Chicago, Chicago, Illinois; and
32Division of Nuclear Medicine, Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania;
44Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland

Tóm tắt

Abstract Cancer cells frequently display high rates of aerobic glycolysis in comparison to their nontransformed counterparts, although the molecular basis of this phenomenon remains poorly understood. Constitutive activity of the serine/threonine kinase Akt is a common perturbation observed in malignant cells. Surprisingly, although Akt activity is sufficient to promote leukemogenesis in nontransformed hematopoietic precursors and maintenance of Akt activity was required for rapid disease progression, the expression of activated Akt did not increase the proliferation of the premalignant or malignant cells in culture. However, Akt stimulated glucose consumption in transformed cells without affecting the rate of oxidative phosphorylation. High rates of aerobic glycolysis were also identified in human glioblastoma cells possessing but not those lacking constitutive Akt activity. Akt-expressing cells were more susceptible than control cells to death after glucose withdrawal. These data suggest that activation of the Akt oncogene is sufficient to stimulate the switch to aerobic glycolysis characteristic of cancer cells and that Akt activity renders cancer cells dependent on aerobic glycolysis for continued growth and survival.

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Cancer Research

Tập 64 Số 11

3892-3899

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