AMPK is a negative regulator of the Warburg Effect and suppresses tumor growth in vivo

By B. Faubert, Gino Boily, Said Izreig, Takla Griss, B. Samborska, Zhifeng Dong, Fanny Dupuy, Christopher Chambers, B. Fuerth, B. Viollet and 5 more. Cell Metabolism, 2012

905 citations recorded by the source corpus.

Summary 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 non-transformed 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 its loss fosters tumor progression in part by regulating cellular metabolic pathways that support cell growth and proliferation.

Subfields: Cancer Research, Molecular Biology, Surgery

View Paper: https://www.semanticscholar.org/paper/9eb0681ede74fd575f2f3ebb7d637141c6502b53

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cancer Research

1. Erika L. Pearce
2. Gabriele Multhoff
3. G. J. Yoshida
4. Russell G. Jones
5. P. Vaupel
6. Cormac T. Taylor
7. M. Poffenberger
8. Chih-Hao Chang

In Molecular Biology

1. G. J. Yoshida
2. Russell G. Jones
3. Gabriele Multhoff
4. P. Vaupel
5. Cormac T. Taylor
6. M. Poffenberger
7. Erika L. Pearce
8. B. Viollet

In Surgery

1. G. J. Yoshida
2. Russell G. Jones
3. Erika L. Pearce
4. B. Viollet

Citations in the corpus

• The energy sensor AMPK regulates T cell metabolic adaptation and effector responses in vivo. (2015, methodology): “GC-MS- and LC-MS-based metabolomics studies were performed using previously described methods (Dupuy et al., 2013; Faubert et al., 2013).”
• Crosstalk between Microbiota-Derived Short-Chain Fatty Acids and Intestinal Epithelial HIF Augments Tissue Barrier Function (2015, positive): “A recent report indicated that activated AMPK is an endogenous inhibitor of the Warburg effect (Faubert et al., 2013), and that butyrate is a potent activator of AMPK in colonic cell lines (Elamin et al., 2013).”
• Fueling Immunity: Insights into Metabolism and Lymphocyte Function (2013, background): “Glycolysis is enhanced in resting AMPKa-deficient T cells (88), consistent with observations that silencing AMPK in tumor cells promotes the Warburg effect (89).”
• Metabolic reprogramming: the emerging concept and associated therapeutic strategies (2015, background): “Moreover, the regulation of adenosine monophosphate-activated protein kinase (AMPK) signal transduction, a sensor of energy status, is intimately connected to the Warburg effect, one form of metabolic reprogramming of cancer cells [34, 35].”
• Revisiting the Warburg effect: historical dogma versus current understanding (2020, background): “4, major mechanisms acting independently or in cooperation to sustain aerobic glycolysis in cancer cells are: (a) hypoxic/normoxic activation of HIF-1 (‘master regulator’, which can also work in concert with epigenetic mechanisms), (b) activation (gain of function) of oncogenes (e.g. cMyc, mTORC1, A”