Role of CK1 in GSK3β-mediated phosphorylation and degradation of Snail

The epithelial to mesenchymal transition (EMT) that occurs during embryonic development has begun to attract attention as a potential mechanism for tumor cell metastasis. Snail is a well-known Zn-finger transcription factor that promotes EMT by repressing E-cadherin expression. It is known that Snail is phosphorylated by GSK3 beta and degraded by beta-TrCP-mediated ubiquitination. Here we described another protein kinase, CK1, whose phosphorylation of Snail is required for the subsequent GSK3 beta phosphorylation. Specific inhibition or depletion of CK1 epsilon inhibits the phosphorylation and degradation of Snail and promotes cell migration, suggesting a central role of CK1 epsilon in the EMT process. Furthermore, our study uncovered distinct roles and steps of Snail phosphorylation by CK1 epsilon and GSK3 beta. Taken together, we identified CK1 epsilon as a new component of the Snail-mediated EMT process, providing insight into the mechanism of human cancer metastasis. Oncogene (2010) 29, 3124-3133; doi: 10.1038/onc.2010.77; published online 22 March 2010