Department of Biochemistry and the Siebens-Drake Medical Research Institute, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, CA.
Cell Adh Migr. 2010 Apr-Jun;4(2):176-9. doi: 10.4161/cam.4.2.10690. Epub 2010 Apr 16.
Epithelial to mesenchymal transition (EMT) is a critical event in embryogenesis and plays a fundamental role in cancer progression and metastasis. Numb has been shown to play an important role in the proper functions of Par protein complex and in cell-cell junctions, both of which are associated with EMT. However, the role of Numb in EMT has not been fully elucidated. Recently, we showed that Numb is capable of binding to both Par3 and E-cadherin. Intriguingly, the interaction of Numb with E-cadherin or the Par protein complex is dynamically regulated by tyrosine phosphorylation induced by HGF or Src. Knockdown of Numb by shRNA in MDCK cells led to a lateral to apical translocation of E-cadherin and beta-catenin, active F-actin polymerization, mis-localization of Par3 and aPKC, a decrease in cell-cell adhesion and an increase in cell migration and proliferation. These data suggest a diverse role for Numb in regulating cell-cell adhesion, polarity and migration during EMT.
上皮-间充质转化（EMT）是胚胎发生中的一个关键事件，在癌症进展和转移中起着重要作用。已经表明 Numb 在 Par 蛋白复合物的正常功能和细胞-细胞连接中发挥重要作用，这两者都与 EMT 有关。然而，Numb 在 EMT 中的作用尚未完全阐明。最近，我们表明 Numb 能够与 Par3 和 E-钙粘蛋白结合。有趣的是，Numb 与 E-钙粘蛋白或 Par 蛋白复合物的相互作用可被 HGF 或 Src 诱导的酪氨酸磷酸化动态调节。在 MDCK 细胞中用 shRNA 敲低 Numb 导致 E-钙粘蛋白和β-连环蛋白从侧向到顶侧易位、活性 F-肌动蛋白聚合、Par3 和 aPKC 的定位错误、细胞-细胞黏附减少以及细胞迁移和增殖增加。这些数据表明 Numb 在 EMT 期间通过调节细胞-细胞黏附、极性和迁移发挥多种作用。
