fig1

Figure 1. A schematic summary illustrating mechanisms targeting Notch in GCSs (see the text for details). (1–3) TME cell populations, secreting a number of factors including Notch ligands, stimulate the transcriptional activity of Notch receptors, thus influencing tumor biology. (4) NICD physically cooperates with β-catenin, Smad proteins, and HIF-1α, thus obtaining the crosstalk among Notch, Wnt, TGF-β, and hypoxia-dependent signaling pathways. (5) Notch-mediated transcriptional activation achieves the NICD degradation through phosphorylation of NICD, mediated by CDK8 and targeted for proteasome-mediated degradation. (6) Decrease of EGFR expression due to Numb-mediated endocytosis.