Here we show a role for the TRPM7 kinase domain in pancreatic carcinogenesis since (i) TRPM7 kinase domain is required to maintain a mesenchymal phenotype in PDAC cells, (ii) TRPM7 and PAK1 interact in the same protein complexes in PDAC cells, (iii) TRPM7 kinase domain is required for carcinogenesis and cancer cell dissemination in vivo, and iv) the role of TRPM7 kinase is cell specific and may depend on the KRAS oncogene mutation status. Here, KRAS is linked to cancer.