DYRK2 controls the epithelial–mesenchymal transition in breast cancer by degrading Snail

•DYRK2 expression is maintained at low level by the proteolytic machinery in progressing tumors.•Diminished expression of DYRK2 leads to accumulation of Snail to promote EMT and invasion.•DYRK2 phosphorylates Snail at Ser104 and decreases Snail protein stability via the ubiquitin-proteasome pathway.•Low expression of DYRK2 is correlated with poor outcome in breast cancer patients.

The epithelial–mesenchymal transition (EMT) plays a fundamental role in the early stages of breast cancer invasion. Snail, a zinc finger transcriptional repressor, is an important regulator of EMT. Snail is phosphorylated by GSK3β and is subsequently degraded by βTrCP-mediated ubiquitination. We identified an additional kinase, DYRK2, that regulates Snail stability. Knockdown of DYRK2 promoted EMT and cancer invasion in vitro and in vivo. Consistent with these results, DYRK2 was found to be down-regulated in human breast cancer tissue. Patients with low DYRK2-expressing tumors had a worse outcome than those with high DYRK2-expressing tumors. These findings revealed that DYRK2 regulates cancer invasion and metastasis by degrading Snail.