Fig. 8. Schematic representation of the antimetastatic signaling promoted by activation of Kv11.1.

1) In normal epithelial cells, β-catenin is in complex with adhesive proteins (e.g., E-cadherin) and promotes cell–cell contact. GSK3⍰-dependent phosphorylation controls β-catenin degradation while AKT-dependent phosphorylation controls β-catenin nuclear translocation. 2) In cancer cells, the Wnt-dependent signaling arrests β-catenin degradation by inhibiting GSK3β activity. Consequently, upon AKT phosphorylation β-catenin translocates to the nucleus and transcribes for genes controlling epithelial to mesenchymal transition (EMT) and migration. 3) Activation of the Kv11.1 promotes epithelial phenotype in mesenchymal cancer cells (MET) by inhibiting GSK3β-dependent β-catenin degradation and AKT-dependent nuclear translocation of β-catenin, producing β-catenin accumulation at the surface membrane and therefore, improving cell–cell contact