title: Akt stimulates aerobic glycolysis in cancer cells.
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.
authors.affiliation: Department of Cancer Biology, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Elstrom
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Bauer
authors.forename: Monica
authors.initials: M
authors.lastname: Buzzai
authors.forename: Robyn
authors.initials: R
authors.lastname: Karnauskas
authors.forename: Marian H
authors.initials: MH
authors.lastname: Harris
authors.forename: David R
authors.initials: DR
authors.lastname: Plas
authors.forename: Hongming
authors.initials: H
authors.lastname: Zhuang
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Cinalli
authors.forename: Abass
authors.initials: A
authors.lastname: Alavi
authors.forename: Charles M
authors.initials: CM
authors.lastname: Rudin
authors.forename: Craig B
authors.initials: CB
authors.lastname: Thompson
mesh_terms: D000332:Aerobiosis; D000818:Animals; D045744:Cell Line, Tumor; D004789:Enzyme Activation; D005909:Glioblastoma / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D006019:Glycolysis; D006801:Humans; D007938:Leukemia / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D014162:Transfection
chemical_list: D005947:Glucose; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; C494918:AKT1 protein, human