Recent reports have proposed the existence of an intricate connection between TRPV4 activation and the tumor dynamic microenvironment, suggesting that during this complex process, TRPV4 channels sensitized by different stimuli, including matrix stiffness, are rapidly activated and became critical for the arrangement of the metastatic cascade in a plethora of tumors, such as breast, endometrial, gastric, and colon cancer, as well as in the induction of the migratory phenotype in melanoma cells [67,68]. The gene discussed is TRPV4; the disease is melanoma.