Wnt-mediated protein stabilization ensures proper mitotic microtubule assembly and chromosome segregation

Wnt signaling stimulates cell proliferation by promoting the G1/S transition of the cell cycle through β-catenin/TCF4-mediated gene transcription. However, Wnt signaling peaks in mitosis and contributes to the stabilization of proteins other than β-catenin, a pathway recently introduced as Wnt-dependent stabilization of proteins (Wnt/STOP). Here, we show that Wnt/STOP regulated by basal Wnt signaling during a normal cell cycle is required for proper spindle microtubule assembly and for faithful chromosome segregation during mitosis. Consequently, inhibition of basal Wnt signaling results in increased microtubule assembly rates, abnormal mitotic spindle formation and the induction of aneuploidy in human somatic cells.