DYRK2 通过降解 Snail 来控制乳腺癌中的上皮-间充质转化。
DYRK2 controls the epithelial-mesenchymal transition in breast cancer by degrading Snail.
机构信息
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.
出版信息
Cancer Lett. 2013 Oct 10;339(2):214-25. doi: 10.1016/j.canlet.2013.06.005. Epub 2013 Jun 18.
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.
上皮-间充质转化 (EMT) 在乳腺癌侵袭的早期阶段起着至关重要的作用。锌指转录阻遏物 Snail 是 EMT 的重要调节因子。Snail 可被 GSK3β 磷酸化，随后被 βTrCP 介导的泛素化降解。我们鉴定出一种额外的激酶 DYRK2，它可以调节 Snail 的稳定性。DYRK2 的敲低促进了 EMT 和体外及体内的癌症侵袭。与这些结果一致的是，在人类乳腺癌组织中发现 DYRK2 下调。肿瘤中 DYRK2 表达水平低的患者比 DYRK2 表达水平高的患者预后更差。这些发现表明，DYRK2 通过降解 Snail 来调节癌症的侵袭和转移。
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