AMPK is a negative regulator of the warburg effect and suppresses tumor growth in vivo

Brandon Faubert, Gino Boily, Said Izreig, Takla Griss, Bozena Samborska, Zhifeng Dong, Fanny Dupuy, Christopher Chambers, Benjamin J. Fuerth, Benoit Viollet, Orval A. Mamer, Daina Avizonis, Ralph J. Deberardinis, Peter M. Siegel, Russell G. Jones

Research output: Contribution to journalArticlepeer-review

484 Scopus citations

Abstract

AMPK is a metabolic sensor that helps maintain cellular energy homeostasis. Despite evidence linking AMPK with tumor suppressor functions, the role of AMPK in tumorigenesis and tumor metabolism is unknown. Here we show that AMPK negatively regulates aerobic glycolysis (the Warburg effect) in cancer cells and suppresses tumor growth in vivo. Genetic ablation of the α1 catalytic subunit of AMPK accelerates Myc-induced lymphomagenesis. Inactivation of AMPKα in both transformed and nontransformed cells promotes a metabolic shift to aerobic glycolysis, increased allocation of glucose carbon into lipids, and biomass accumulation. These metabolic effects require normoxic stabilization of the hypoxia-inducible factor-1α (HIF-1α), as silencing HIF-1α reverses the shift to aerobic glycolysis and the biosynthetic and proliferative advantages conferred by reduced AMPKα signaling. Together our findings suggest that AMPK activity opposes tumor development and that its loss fosters tumor progression in part by regulating cellular metabolic pathways that support cell growth and proliferation.

Original languageEnglish (US)
Pages (from-to)113-124
Number of pages12
JournalCell Metabolism
Volume17
Issue number1
DOIs
StatePublished - Jan 8 2013

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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