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Loss of AMPKα2 promotes melanoma tumor growth and brain metastasis


ABSTRACT: Summary AMP-activated protein kinase (AMPK) is a critical cellular energy sensor at the interface of metabolism and cancer. However, the role of AMPK in carcinogenesis remains unclear. Here, through analysis of the TCGA melanoma dataset, we found that PRKAA2 gene that encodes the α2 subunit of AMPK is mutated in ∼9% of cutaneous melanomas, and these mutations tend to co-occur with NF1 mutations. Knockout of AMPKα2 promoted anchorage-independent growth of NF1-mutant melanoma cells, whereas ectopic expression of AMPKα2 inhibited their growth in soft agar assays. Moreover, loss of AMPKα2 accelerated tumor growth of NF1-mutant melanoma and enhanced their brain metastasis in immune-deficient mice. Our findings support that AMPKα2 serves as a tumor suppressor in NF1-mutant melanoma and suggest that AMPK could be a therapeutic target for treating melanoma brain metastasis. Graphical abstract Highlights • AMPKα2 mutations frequently occur in melanomas, often together with NF1 mutations• Loss of AMPKα2 accelerated tumor growth of NF1-mutant melanoma in nude mice• AMPKα2 levels are lower in melanoma brain metastasis than extracranial metastases• Loss of AMPKα2 enhanced brain metastasis of NF1-mutant melanoma in mice Molecular Genetics ; Biological database; Cancer.

SUBMITTER: Yuan P 

PROVIDER: S-EPMC10197146 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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