NOTCH1 and central nervous system cancer: PI3k/Akt signaling regulates angiogenesis by affecting expressions of VEGF, HIF-1α, and MMP9 [57,76,77,78,79].Activation of PI3k by Notch1 also stimulates the signaling pathways of MMP9, β-catenin, and NF-κB, which increases the migratory, invasiveness, and angiogenic properties of glioma cells [17,77,78].