Loss of AMPK2 promotes melanoma tumor growth and brain metastasis

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 alpha 2 subunit of AMPK is mutated in similar to-9% of cutaneous melanomas, and these mutations tend to co-occur with NF1 mutations. Knockout of AMPK alpha 2 promoted anchorage-independent growth of NF1-mutant melanoma cells, whereas ectopic expression of AMPK alpha 2 inhibited their growth in soft agar assays. Moreover, loss of AMPK alpha 2 accelerated tumor growth of NF1-mutant melanoma and enhanced their brain metastasis in im-mune-deficient mice. Our findings support that AMPK alpha 2 serves as a tumor sup-pressor in NF1-mutant melanoma and suggest that AMPK could be a therapeutic target for treating melanoma brain metastasis.