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Evidence of cancer‐promoting roles for AMPK and related kinases
Author(s) -
Monteverde Tiziana,
Muthalagu Nathiya,
Port Jennifer,
Murphy Daniel J.
Publication year - 2015
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.13534
Subject(s) - ampk , kinase , microbiology and biotechnology , protein kinase a , amp activated protein kinase , context (archaeology) , catabolism , biology , chemistry , biochemistry , enzyme , paleontology
The discovery that the 5′ AMP ‐activated protein kinase ( AMPK ) serves to link the tumour suppressors LKB 1 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 pro‐ or 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 LKB 1 and studies are beginning to reveal a similar duality of roles in cancer for other members of the AMPK ‐related kinase family.