Abstract

The mechanosensitive ion channel PIEZO1 is a critical mediator of cellular responses to mechanical stimuli, and its dysregulation has been implicated in the progression of various cancers, including melanoma. This study investigates the functional role of the PIEZO1 channel in the cell motility and migration of aggressive human melanoma SK-MEL-2 cells. We hypothesized that PIEZO1 activity modulates the metastatic potential of these cells. Using a combination of pharmacological activation with Yoda1, calcium imaging, and functional assays such as wound healing and transwell migration, we assessed the impact of PIEZO1 on cell behavior. Our results confirm the functional expression of PIEZO1 in SK-MEL-2 cells and demonstrate that its activation significantly inhibits both cell motility and directional migration. Mechanistically, this effect is likely mediated by PIEZO1-dependent calcium influx, which may interfere with the cytoskeletal dynamics necessary for migration. These findings suggest that PIEZO1 acts as a potential negative regulator of metastatic behavior in aggressive melanoma, offering a novel therapeutic target for modulating the mechanical cues that drive cancer cell dissemination. Further research is warranted to fully elucidate the downstream signaling pathways involved.