Evidence of cancer‐promoting roles for AMPK and related kinases. (19th October 2015)

• Record Type: Journal Article
• Authors: Monteverde, Tiziana; Muthalagu, Nathiya; Port, Jennifer; Murphy, Daniel J.
• Is Part Of: FEBS journal. Volume 282:Number 24(2015)
• Page Start: 4658
• Page End: 4671
• Publication Date: 2015-10-19
• Subjects: AMPK -- AMPK related kinases -- ATP homeostasis -- CaMKKB -- cancer genetics -- cancer metabolism -- LKB1 -- MARK -- NUAK -- reactive oxygen species; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pathology, Molecular -- Periodicals; 572
• DOI: 10.1111/febs.13534
• Languages: English
• ISSNs: 1742-464X

Abstract

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. Abstract : AMPK is implicated in tumour suppression, largely due to its role in attenuation on MTORC1‐driven cell growth. However AMPK may also protect tumour cells from cytotoxic levels of oxidative and energetic stress, in particular in the context of advanced solid tissue cancers. AMPK‐related kinases (ARKs) may similarly have both tumour‐promoting and tumour suppressing functions.