Siva1 Inhibits Epithelial-mesenchymal Transition And Metastasis Of Tumor Cells

Epithelial-mesenchymal transition (EMT) enables epithelial cells to acquire motility and invasiveness that are characteristic of mesenchymal cells. It plays an important role in development and in tumor cell metastasis. However, the mechanisms of EMT and their dysfunction in cancer cells are still not well understood.In our study, we report that Sival interacts with stathmin, a microtubule destabilizer. Sival inhibits stathmin's activity directly as well as through Ca2+/calmodulin-dependent protein kinaseâ…¡(CaMKâ…¡)-mediated phosphorylation of stathmin at Ser16. Via the inhibition of stathmin, Sival enhances the formation of microtubules and impedes focal adhesion assembly, cell migration, and EMT. Low levels of Sival and Ser16-phosphorylated stathmin correlate with high metastatic states of human breast cancer cells. Furthermore, knockdown of Sival promotes cancer dissemination in mouse models. These results suggest that microtubule dynamics are critical for EMT. Furthermore, they reveal an important role for Sival in suppressing cell migration and EMT, and indicate that down-regulation of Sival may contribute to tumor cell metastasis.In summary, these data suggest that Sival plays important role in EMT and tumor metastasis.