Affiliation
Transcriptional Networks in Lung Cancer Group, Cancer Research UK Manchester Institute, The University of Manchester, Manchester, UK.Issue Date
2021
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Show full item recordAbstract
AMP-activated protein kinase (AMPK) is a critical sensor of energy status that coordinates cell growth with energy balance. In non-small cell lung cancer (NSCLC) the role of AMPKα is controversial and its contribution to lung carcinogenesis is not well-defined. Furthermore, it remains largely unknown whether long non-coding RNAs (lncRNAs) are involved in the regulation of AMPK-mediated pathways. Here, we found that loss of AMPKα in combination with activation of mutant KRASG12D increased lung tumour burden and reduced survival in KrasLSLG12D/+/AMPKαfl/fl mice. In agreement, functional in vitro studies revealed that AMPKα silencing increased growth and migration of NSCLC cells. In addition, we identified an AMPKα-modulated lncRNA, KIMAT1 (ENSG00000228709), which in turn regulates AMPKα activation by stabilizing the lactate dehydrogenase B (LDHB). Collectively, our study indicates that AMPKα loss promotes KRAS-mediated lung tumorigenesis and proposes a novel KRAS/KIMAT1/LDHB/AMPKα axis that could be exploited for therapeutic purposes.Citation
La Montagna M, Shi L, Magee P, Sahoo S, Fassan M, Garofalo M. AMPKα loss promotes KRAS-mediated lung tumorigenesis. Cell Death Differ. 2021 May 26.Journal
Cell Death and DifferentiationDOI
10.1038/s41418-021-00777-0PubMed ID
34040167Additional Links
https://dx.doi.org/10.1038/s41418-021-00777-0Type
ArticleLanguage
enae974a485f413a2113503eed53cd6c53
10.1038/s41418-021-00777-0
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