Molecular Pathways: Is AMPK a Friend or a Foe in Cancer?

The AMP-activated protein kinase (AMPK) is a sensor of cellular energy status expressed in essentially all eukaryotic cells. Once activated by energetic stress via a mechanism that detects increases in AMP:ATP and ADP:ATP ratios, AMPK acts to restore energy homeostasis by switching on catabolic path...

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Bibliographic Details
Published in:Clinical cancer research 2015-09, Vol.21 (17), p.3836-3840
Main Author: Hardie, D Grahame
Format: Article
Language:English
Subjects:
AMP-Activated Protein Kinases - genetics
AMP-Activated Protein Kinases - metabolism
Animals
Humans
Neoplasms - genetics
Neoplasms - metabolism
Signal Transduction
Translational Research, Biomedical - trends
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Summary:The AMP-activated protein kinase (AMPK) is a sensor of cellular energy status expressed in essentially all eukaryotic cells. Once activated by energetic stress via a mechanism that detects increases in AMP:ATP and ADP:ATP ratios, AMPK acts to restore energy homeostasis by switching on catabolic pathways that generate ATP, while switching off ATP-consuming processes, including anabolic pathways required for cell growth and proliferation. AMPK activation promotes the glucose-sparing, oxidative metabolism utilized by most quiescent cells, rather than the rapid glucose uptake and glycolysis used by most proliferating cells. Numerous pharmacologic activators of AMPK are known, including drugs in long use such as salicylate and metformin, and there is evidence that regular use of either of the latter provides protection against development of cancer. Tumor cells appear to be under selection pressure to downregulate AMPK, thus limiting its restraining influence on cell growth and proliferation, and several interesting mechanisms by which this occurs are discussed. Paradoxically, however, a complete loss of AMPK function, which appears to be rare in human cancers, may be deleterious to survival of tumor cells. AMPK can therefore be either a friend or a foe in cancer, depending on the context.
ISSN:1078-0432
1557-3265
DOI:10.1158/1078-0432.ccr-14-3300