Molecular Pathways: Is AMPK a Friend or a Foe in Cancer?
Molecular Pathways: Is AMPK a Friend or a Foe in Cancer?
复制标题
DOI：
10.1158/1078-0432.ccr-14-3300
复制
发表时间：
2015-09-01
期刊：
影响因子：
--
通讯作者：
Hardie DG
中科院分区：
文献类型：
--
作者：
Hardie DG
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 pharmacological 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 down-regulate 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 either be a friend and a foe in cancer, depending on the context.
