Endothelial-to-Mesenchymal Transition (EndoMT): Roles in Tumorigenesis, Metastatic Extravasation and Therapy Resistance

Figure 4

Notch induction of EndoMT. Notch receptors’ family interacts with diverse ligands via a cell-to-cell contact mechanism. The signal is mediated by the Notch intracellular domain (NICD) through the nucleus to activate a complex of inducers (RBPJ/CBF1/Su(H)) which in turn activates the transcription of genes implicated in EndoMT. This complex also stabilizes the Snail protein. The Notch pathway crosstalks with several other pathways: NICD increases the Akt 2 expression which inhibits GSK-3β. NICD also activates ERK 1/2, which activates RSK leading to GSK-3β downregulation. The nuclear Notch complex also interacts with β-catenin, increasing its transcription activity.