Evidence of cancer-promoting roles for AMPK and related kinases

Monteverde, T., Muthalagu, N., Port, J. and Murphy, D. (2015) Evidence of cancer-promoting roles for AMPK and related kinases. FEBS Journal, 282(24), pp. 4658-4671. (doi: 10.1111/febs.13534) (PMID:26426570)

[img]
Preview
Text
116103.pdf - Accepted Version

1MB

Abstract

The discovery that the 5′AMP-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 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 LKB1 and studies are beginning to reveal a similar duality of roles in cancer for other members of the AMPK-related kinase family.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Murphy, Professor Daniel
Authors: Monteverde, T., Muthalagu, N., Port, J., and Murphy, D.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:FEBS Journal
Publisher:Wiley-Blackwell Publishing Ltd.
ISSN:1742-464X
ISSN (Online):1742-4658
Copyright Holders:Copyright © 2016 Wiley-Blackwell Publishing Ltd.
First Published:First published in FEBS Journal 282(24):4658-4671
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher.

University Staff: Request a correction | Enlighten Editors: Update this record