In this study we demonstrate, through in vitro and ex vivo approaches, a direct involvement of the iPolyP/TRPM8 axis in the EMT process, which ultimately confers migratory properties to colorectal cancer cells, as well as a novel and unexpected involvement in the inflammatory pathway through the induction and secretion of the NLRP3 inflammasome-derived IL-1β, further enhancing CRC cell migration. Here, NLRP3 is linked to colorectal carcinoma.