AMPKα loss promotes KRAS-mediated lung tumorigenesis
Manuela La Montagna1,2, Lei Shi1,2, Peter Magee1,2
1Transcriptional Networks in Lung Cancer Group, Cancer Research UK Manchester Institute, The University of Manchester, Manchester, UK.
Cell Death and Differentiation
|May 27, 2021
Summary
Loss of AMPKα promotes KRAS-driven lung cancer by affecting cell growth and migration. A novel axis involving KIMAT1 and LDHB regulates AMPKα activation, offering potential therapeutic targets for non-small cell lung cancer.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- AMP-activated protein kinase (AMPK) is a key energy sensor influencing cell growth.
- The role of AMPKα in non-small cell lung cancer (NSCLC) and its link to long non-coding RNAs (lncRNAs) are not well understood.
Purpose of the Study:
- To investigate the role of AMPKα in KRAS-driven lung carcinogenesis.
- To identify lncRNAs involved in AMPK-mediated pathways in NSCLC.
- To elucidate a novel regulatory axis in lung tumorigenesis.
Main Methods:
- Utilized KrasLSLG12D/+/AMPKαfl/fl mouse models to assess tumor burden and survival.
- Performed in vitro studies involving AMPKα silencing in NSCLC cells.
- Identified and characterized the lncRNA KIMAT1 and its interaction with LDHB.
Main Results:
- Loss of AMPKα combined with mutant KRASG12D significantly increased lung tumor burden and reduced survival in mice.
- AMPKα silencing enhanced NSCLC cell growth and migration in vitro.
- Discovered KIMAT1 as an AMPKα-modulated lncRNA that stabilizes LDHB, influencing AMPKα activation.
Conclusions:
- AMPKα loss promotes KRAS-mediated lung tumorigenesis.
- A novel regulatory axis (KRAS/KIMAT1/LDHB/AMPKα) is proposed.
- This axis represents a potential therapeutic target for NSCLC.
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