Figure 2

Schematic representation of Notch signaling related to EMT. Upon ligand binding, Notch undergoes two proteolytic cleavages by ADAM and γ-secretase complex, leading to the release of Notch-ICD and its translocating to the nucleus. In the nucleus Notch-ICD interacts with CSL and activates numerous downstream target genes: upregulation of snail, slug, zeb1, cyclinD1 and Smad; downregultion of E-cadherin, p21, etc. to induce EMT. (Notch-ECD, the extracellular domain of Notch; Notch-ICD, the intracellular domain of Notch; ADAM, a disintegrin and metalloproteinase; CSL, CBF-1/suppressor of hairless/Lag1).