@article{c535199bf8cd4ad8b9780e9248b4c2bb,
title = "AMPK is a negative regulator of the warburg effect and suppresses tumor growth in vivo",
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.",
author = "Brandon Faubert and Gino Boily and Said Izreig and Takla Griss and Bozena Samborska and Zhifeng Dong and Fanny Dupuy and Christopher Chambers and Fuerth, {Benjamin J.} and Benoit Viollet and Mamer, {Orval A.} and Daina Avizonis and Deberardinis, {Ralph J.} and Siegel, {Peter M.} and Jones, {Russell G.}",
note = "Funding Information: We would like to thank Connie Krawczyk, Arnim Pause, Jerry Pelletier, Francis Robert, David Shackelford, and Leah Donnelly for technical and administrative help. We are also grateful to Kimberly Wong, Alon Morantz, Valerie Laurin, and Luciana Tonelli for animal expertise. We acknowledge salary support from Canadian Institutes of Health Research (CIHR) (to B.F. and R.G.J.), the Fonds de recherche du Qu{\'e}bec-Sant{\'e} (FRQS) (to G.B. and P.M.S.), the McGill Integrated Cancer Research Training Program (MICRTP) (to B.F, G.B, and T.G.), and the Research Institute of the McGill University Health Centre (RI-MUHC) (to F.D.). R.J.D. was supported by National Institutes of Health grant R01CA157996. This work was supported by grants to R.G.J. from the CIHR (MOP-93799), Canadian Cancer Society (700586), and Terry Fox Research Foundation (TEF-116128). ",
year = "2013",
month = jan,
day = "8",
doi = "10.1016/j.cmet.2012.12.001",
language = "English (US)",
volume = "17",
pages = "113--124",
journal = "Cell Metabolism",
issn = "1550-4131",
publisher = "Cell Press",
number = "1",
}