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 journalArticle

424 Citations (Scopus)

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

Fingerprint

AMP-Activated Protein Kinases
Growth
Neoplasms
Glycolysis
Hypoxia-Inducible Factor 1
Metabolic Networks and Pathways
Biomass
Catalytic Domain
Carcinogenesis
Homeostasis
Carbon
Cell Proliferation
Lipids
Glucose

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Physiology

Cite this

Faubert, B., Boily, G., Izreig, S., Griss, T., Samborska, B., Dong, Z., ... Jones, R. G. (2013). AMPK is a negative regulator of the warburg effect and suppresses tumor growth in vivo. Cell Metabolism, 17(1), 113-124. https://doi.org/10.1016/j.cmet.2012.12.001

AMPK is a negative regulator of the warburg effect and suppresses tumor growth in vivo. / Faubert, Brandon; Boily, Gino; Izreig, Said; Griss, Takla; Samborska, Bozena; Dong, Zhifeng; Dupuy, Fanny; Chambers, Christopher; Fuerth, Benjamin J.; Viollet, Benoit; Mamer, Orval A.; Avizonis, Daina; Deberardinis, Ralph J.; Siegel, Peter M.; Jones, Russell G.

In: Cell Metabolism, Vol. 17, No. 1, 08.01.2013, p. 113-124.

Research output: Contribution to journalArticle

Faubert, B, Boily, G, Izreig, S, Griss, T, Samborska, B, Dong, Z, Dupuy, F, Chambers, C, Fuerth, BJ, Viollet, B, Mamer, OA, Avizonis, D, Deberardinis, RJ, Siegel, PM & Jones, RG 2013, 'AMPK is a negative regulator of the warburg effect and suppresses tumor growth in vivo', Cell Metabolism, vol. 17, no. 1, pp. 113-124. https://doi.org/10.1016/j.cmet.2012.12.001
Faubert B, Boily G, Izreig S, Griss T, Samborska B, Dong Z et al. AMPK is a negative regulator of the warburg effect and suppresses tumor growth in vivo. Cell Metabolism. 2013 Jan 8;17(1):113-124. https://doi.org/10.1016/j.cmet.2012.12.001
Faubert, Brandon ; Boily, Gino ; Izreig, Said ; Griss, Takla ; Samborska, Bozena ; Dong, Zhifeng ; Dupuy, Fanny ; Chambers, Christopher ; Fuerth, Benjamin J. ; Viollet, Benoit ; Mamer, Orval A. ; Avizonis, Daina ; Deberardinis, Ralph J. ; Siegel, Peter M. ; Jones, Russell G. / AMPK is a negative regulator of the warburg effect and suppresses tumor growth in vivo. In: Cell Metabolism. 2013 ; Vol. 17, No. 1. pp. 113-124.
@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.}",
year = "2013",
month = "1",
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",

}

TY - JOUR

T1 - AMPK is a negative regulator of the warburg effect and suppresses tumor growth in vivo

AU - Faubert, Brandon

AU - Boily, Gino

AU - Izreig, Said

AU - Griss, Takla

AU - Samborska, Bozena

AU - Dong, Zhifeng

AU - Dupuy, Fanny

AU - Chambers, Christopher

AU - Fuerth, Benjamin J.

AU - Viollet, Benoit

AU - Mamer, Orval A.

AU - Avizonis, Daina

AU - Deberardinis, Ralph J.

AU - Siegel, Peter M.

AU - Jones, Russell G.

PY - 2013/1/8

Y1 - 2013/1/8

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84872159532&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84872159532&partnerID=8YFLogxK

U2 - 10.1016/j.cmet.2012.12.001

DO - 10.1016/j.cmet.2012.12.001

M3 - Article

C2 - 23274086

AN - SCOPUS:84872159532

VL - 17

SP - 113

EP - 124

JO - Cell Metabolism

JF - Cell Metabolism

SN - 1550-4131

IS - 1

ER -