Atypical function of a centrosomal module in WNT signalling drives contextual cancer cell motility

Centrosomescontrol cell motility, polarity and migration that is thought to be mediated by their microtubule-organizing capacity. Here we demonstrate that WNT signalling drives a distinct form of non-directional cell motilitythat requires a key centrosomemodule, but not microtubules or centrosomes. Upon exosomemobilization of PCP-proteins, we show that DVL2 orchestrates recruitment of a CEP192- PLK4/AURKB complex to the cell cortexwhere PLK4/AURKB act redundantly to drive protrusive activity and cell motility. This is mediated by coordination of formin-dependent actin remodellingthrough displacement of cortically localized DAAM1for DAAM2. Furthermore, abnormal expression of PLK4, AURKB and DAAM1is associated with poor outcomes in breast and bladder cancers. Thus, a centrosomalmodule plays an atypical function in WNT signalling and actin nucleation that is critical for cancer cell motilityand is associated with more aggressive cancers. These studies have broad implications in how contextual signalling controls distinct modes of cell migration.