黑色素瘤是一种高度侵袭性癌症，具有快速转移的独特能力，其基本推动力是由于异常细胞活动行为。因此，发现“移行抑制剂”靶点，特别是在转移期间控制黑色素瘤细胞侵入和扩散的靶点，是非常重要的。在这里，我们揭示了质膜TRPV2钙通道的突出表达，是黑色素瘤肿瘤的一个独特特征，直接与黑色素瘤转移扩散相关。在体内和体外，TRPV2活性足以赋予细胞迁移和侵袭潜力，而相反地，在高度转移性黑色素瘤细胞中，TRPV2沉默则可以预防侵略性行为。在侵袭性黑色素瘤细胞中，TRPV2通道定位在前缘，处于动态新生粘附状态，并调节钙介导的卡尔潘的活性和随之而来的黏附蛋白talin的剪切，以及F-actin的组织。在人类黑色素瘤组织中，TRPV2的过度表达与恶性肿瘤和不良预后相关，有着生物标记潜力。因此，通过调节粘附和运动，机械敏感的TRPV2通道控制黑色素瘤细胞的浸润性，突显了治疗转移性黑色素瘤中的新治疗选择。©2023作者。根据CC BY 4.0许可证发布。

Melanoma is a highly aggressive cancer endowed with a unique capacity of rapidly metastasizing, which is fundamentally driven by aberrant cell motility behaviors. Discovering "migrastatics" targets, specifically controlling invasion and dissemination of melanoma cells during metastasis, is therefore of primary importance. Here, we uncover the prominent expression of the plasma membrane TRPV2 calcium channel as a distinctive feature of melanoma tumors, directly related to melanoma metastatic dissemination. In vitro as well as in vivo, TRPV2 activity is sufficient to confer both migratory and invasive potentials, while conversely TRPV2 silencing in highly metastatic melanoma cells prevents aggressive behavior. In invasive melanoma cells, TRPV2 channel localizes at the leading edge, in dynamic nascent adhesions, and regulates calcium-mediated activation of calpain and the ensuing cleavage of the adhesive protein talin, along with F-actin organization. In human melanoma tissues, TRPV2 overexpression correlates with advanced malignancy and poor prognosis, evoking a biomarker potential. Hence, by regulating adhesion and motility, the mechanosensitive TRPV2 channel controls melanoma cell invasiveness, highlighting a new therapeutic option for migrastatics in the treatment of metastatic melanoma.© 2023 The Authors. Published under the terms of the CC BY 4.0 license.