Abstract Several processes occur during tumor development including changes in cell morphology, a reorganization of the expression and distribution of the cytoskeleton proteins as well as ion channels. If cytoskeleton proteins and ion channels have been widely investigated in understanding cancer mechanisms, the interaction between these two elements and the identification of the associated signaling pathways are only beginning to emerge. In this review, we summarize the work published over the past 15 years relating to the roles played by ion channels in these mechanisms of reorganization of the cellular morphology, essential to metastatic dissemination, both through the physical interactions with elements of the cytoskeleton and by intracellular signaling pathways involved.