TMEM16A inhibition suppresses melanoma metastasisOA

As a highly aggressive malignancy arising from melanocytes,malignant melanoma accounts for the majority of skin cancerrelated deaths worldwide.Metastases,particularly lung and brain metastases,contribute significantly to mortality[1].Although targeted therapy(BRAF/MEK inhibitors)and immunotherapy(checkpoint inhibitors)have greatly improved the overall survival of patients,drug resistance and toxicity remain major clinical challenges[2,3].Therefore,exploring new approaches to combat melanoma metastasis is imperative.Melanoma metastasis involves multiple processes,including phenotype switching(epithelialmesenchymal transition,EMT),migration,invasion and infiltration[4].Phenotype switching occurs at the early stage of metastasis and is characterized by the downregulation of epithelial markers(e.g.,E-cadherin)and the upregulation of mesenchymal markers(e.g.,Ncadherin and Vimentin).Metastasis depends on highly regulated and complex remodeling of the tumor microenvironment formed by cells as well as by biochemical and biophysical components of the extracellular matrix(ECM)and their intricate interactions within and around a solid tumor mass[5].These processes are primarily mediated by the altered expression of metastasis-associated genes,and targeting the expression of these genes may be a promising strategy for inhibitingmelanoma metastasis.