Akt stimulates aerobic glycolysis in cancer cells

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 cell...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2004-06, Vol.64 (11), p.3892-3899
Main Authors: ELSTROM, Rebecca L, BAUER, Daniel E, THOMPSON, Craig B, BUZZAI, Monica, KARNAUSKAS, Robyn, HARRIS, Marian H, PLAS, David R, HONGMING ZHUANG, CINALLI, Ryan M, ALAVI, Abass, RUDIN, Charles M
Format: Article
Language:English
Subjects:
Aerobiosis
Animals
Antineoplastic agents
Biological and medical sciences
Cell Line, Tumor
Enzyme Activation
Glioblastoma - enzymology
Glioblastoma - genetics
Glioblastoma - metabolism
Glucose - metabolism
Glucose - pharmacology
Glycolysis
Humans
Leukemia - enzymology
Leukemia - genetics
Leukemia - metabolism
Medical sciences
Mice
Pharmacology. Drug treatments
Phosphatidylinositol 3-Kinases - metabolism
Protein-Serine-Threonine Kinases - genetics
Protein-Serine-Threonine Kinases - metabolism
Proto-Oncogene Proteins - genetics
Proto-Oncogene Proteins - metabolism
Proto-Oncogene Proteins c-akt
Transfection
Tumors
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Summary: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.
ISSN:0008-5472
1538-7445
DOI:10.1158/0008-5472.can-03-2904