• TMEM16A knockdown significantly reduces melanoma cell migration, invasion, and adhesion in vitro, as shown by wound healing, transwell, and Matrigel assays.
• Pharmacological inhibition of TMEM16A with T16inh-A01 and Caccinh-A01 mimics the effects of knockdown, confirming its role as a key mediator of metastatic processes.
• TMEM16A promotes melanoma metastasis by upregulating mesenchymal markers (N-cadherin, Vimentin) and MMP9, which are critical for EMT and ECM remodeling.
• In a pulmonary metastasis mouse model, TMEM16A knockdown completely prevented visible lung nodules, indicating that TMEM16A inhibition is a promising therapeutic strategy for suppressing melanoma metastasis.