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Cancer Lett. 2013 Oct 10;339(2):214-25. doi: 10.1016/j.canlet.2013.06.005. Epub 2013 Jun 18.

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

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Department of Biochemistry, The Jikei University School of Medicine, Tokyo, Japan; Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan; Department of Anatomy, The Jikei University School of Medicine, Tokyo, Japan.


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.


Breast cancer; DYRK2; E-cadherin; EMT; Snail

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