Loss of AMPKα2 promotes melanoma tumor growth and brain metastasis

Ping Yuan; Da Teng; Evelyn de Groot; Man Li; Sebastian Trousil; Che-Hung Shen; Jason Roszik; Michael A Davies; Y N Vashisht Gopal; Bin Zheng

doi:10.1016/j.isci.2023.106791

Loss of AMPKα2 promotes melanoma tumor growth and brain metastasis

iScience. 2023 Apr 29;26(6):106791. doi: 10.1016/j.isci.2023.106791. eCollection 2023 Jun 16.

Authors

Affiliations

¹ Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.
² Department of Melanoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Abstract

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.

Keywords: Biological database; Cancer; Molecular Genetics.

Abstract

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