@article{898ee291be5c4ac3826db47a5a9abbb0,
title = "Loss of AMPKα2 promotes melanoma tumor growth and brain metastasis",
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",
author = "Ping Yuan and Da Teng and {de Groot}, Evelyn and Man Li and Sebastian Trousil and Shen, {Che Hung} and Jason Roszik and Davies, {Michael A.} and Gopal, {Y. N.Vashisht} and Bin Zheng",
note = "Funding Information: M.A.D. has been a consultant to Roche/Genentech, Array, Pfizer, Novartis, BMS, GSK, Sanofi-Aventis, Vaccinex, Apexigen, Eisai, Iovance, Merck, and ABM Therapeutics, and he has been the PI of research grants to MD Anderson by Roche/Genentech, GSK, Sanofi-Aventis, Merck, Myriad, Oncothyreon, Pfizer, ABM Therapeutics, and LEAD Pharma. Y.N.V.G. has received funding from Calithera Biosciences. Funding Information: We thank Weiling Li, Chan Mu, and members of the Zheng Lab for assistance and helpful discussion on the manuscript. This work is supported by US National Institutes of Health ( NIH , R01CA276448 ) (to B.Z. and Y.N.V.G.); a Sun Pharma-Society for Investigative Dermatology Mid-Career Investigator Award, the Melanoma Research Alliance , and funds from MGH (to B.Z.); and the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation , the AIM at Melanoma Foundation , the MD Anderson SPORE in Melanoma ( NIH/NCI P50CA221703 ), the American Cancer Society and the Melanoma Research Alliance , Cancer Fighters of Houston , the Anne and John Mendelsohn Chair for Cancer Research , and philanthropic contributions to the Melanoma Moon Shots Program of MD Anderson (to M.A.D.). Publisher Copyright: {\textcopyright} 2023 The Author(s)",
year = "2023",
month = jun,
day = "16",
doi = "10.1016/j.isci.2023.106791",
language = "English (US)",
volume = "26",
journal = "iScience",
issn = "2589-0042",
publisher = "Elsevier Inc.",
number = "6",
}