Wnt5a/Dvl2/Rab35/Rac1 Signaling Pathway Regulates The Migration Of Different Breast Cancer Cells

Wnt5a is a member of non-canonical Wnt family. It plays an important role in the process of synapse out and embryonic development, including some types of cancers. Researches about the mechanism of Wnt5a signal pathway in breast cancer cells are still very limited. We previously demonstrated that Wnt5a signaling stimulated the migration of MDA-MB-231 breast cancer cells via activating RhoA, while RhoA activation was not enhanced by Wnt5a in MCF-7 breast cancer cells. In this study, we showed that in the MDA-MB-231 breast cancer cells, in addition to previous experiment, Wnt5a also induced Racl activation by promoting Dvl2 phosphorylation, thus promoted cell migration. While in the MCF-7 breast cancer cells, Wnt5a dose dependently activated Dvl2, Rab35 and Racl and subsequently promoted cell migration, which was, however, abolished by knocking down Wnt5a expression via small interfering RNA (siRNA) transfection. Dvl2 siRNA significantly decreased background and Wnt5a-induced Rab35/Racl activation and, consequently, cell migration. Rab35 short hairpin RNA (shRNA) remarkably inhibited background and Wnt5a-induced Racl activation and cell migration. Additionally, blockade of Rac1 activation with Rac1 siRNA suppressed background and Wnt5a-induced cell migration. Coimmunoprecipitation and immunofiuorescence assays showed that Dvl2 bound to Rab35 in mammalian cells. Taken together, our research demonstrated that Rab35 is required for Wnt5a/Dvl2-induced Racl activation in MCF-7 breast cancer cells, but not in MDA-MB-231 breast cancer cells.