fig1
![Aberrant Notch signaling in gliomas: a potential landscape of actionable converging targets for combination approach in therapies resistance](https://image.oaes.cc/c06c3134-9e45-4751-b19e-69c0825dc1ad/5239.fig.1.jpg)
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.