期刊
FEBS JOURNAL
卷 282, 期 24, 页码 4658-4671出版社
WILEY
DOI: 10.1111/febs.13534
关键词
AMPK; AMPK related kinases; ATP homeostasis; CaMKKB; cancer genetics; cancer metabolism; LKB1; MARK; NUAK; reactive oxygen species
资金
- British Lung Foundation (BLF)
- Worldwide Cancer Research [1198]
- E.C. Marie Curie Actions grant SERPLUC
- Cancer Research UK [22311] Funding Source: researchfish
The discovery that the 50AMP-activated protein kinase (AMPK) serves to link the tumour suppressors LKB1 and the tuberous sclerosis complex and functions to slow macromolecular synthesis through attenuation of the mechanistic target of rapamycin complex 1 revealed a role for AMPK in tumour suppression. On the other hand, the well-recognized role of AMPK in maintaining ATP homeostasis, through suppression of anabolism and promotion of catabolism, as well as the role of AMPK in neutralizing reactive oxygen species, via maintenance of NADPH-dependent reductive capacity, point to tumour-protective roles in the context of metabolic stress, which is a key feature of many solid tumours. A growing number of studies thus suggest a duality of functions for AMPK that are either proor anti-cancer, depending upon context. Importantly, AMPK is composed of three subunits, and multiple isoforms exist for all three, allowing for different permutations to assemble and the potential for specific AMPK complexes to regulate distinct cellular processes. Moreover, certain subunits of the AMPK complex are frequently overexpressed in a spectrum of human cancer types, suggesting an outright oncogenic function for specific AMPK complexes. Adding complexity to this picture, the catalytic AMPK alpha subunits belong to a family of 14 kinases that can all be activated by LKB1 and studies are beginning to reveal a similar duality of roles in cancer for other members of the AMPK-related kinase family.
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