Figure 1.

A model depicting the role of Numb in epithelial-mesenchymal transition (EMT). In epithelial cells, Numb stabilizes both E-cadherin based adherens junctions through a PTB domain binding to NVYY motif on E-cadherin, and Par protein complex on tight junctions by interacting with Par3. During the early stage of EMT, c-Met recruits the tyrosine kinase c-Src upon its activation by HGF. C-Src phosphorylates E-cadherin on the NVYY motif, which leads to dissociation of Numb from E-cadherin and the translocation of E-cadherin to an apical domain. Numb forms a complex with phosphorylated aPKC and Par6, whereas phosphorylated Par3 is transported into the nucleus. Enhanced F-actin polymerization, together with reduced cell-cell adhesions, promotes the transition to mesenchymal cells.