Figure 7. Regulation of Notch Signaling by Vasorin.

(A) Tumorsphere formation from GSCs (4121 and 3691) transduced with Flag-NICD1 in the setting of reduced Vasorin. GSCs were cultured under hypoxic conditions (1% O₂). Quantification of tumorspheres (right).

(B) qRT-PCR of Vasorin and Notch target genes in GSCs expressing Flag-NICD1 or vector control in the background of shNT or shVasorin knockdown.

(C) Bioluminescence imaging of GBM xenografts derived from GSCs expressing luciferase and either shNT or shVasorin in combination with vector control or Flag-NICD1. Images from animals on day 26 after GSC intracranial transplantation are shown.

(D) Kaplan-Meier survival curves of mice implanted with GSCs (4121) treated as described in (C). Significance testing by log rank test.

(E) Model of membranous Notch1 regulation by Vasorin. Under normoxic conditions, Vasorin expression is low. Numb binds Notch1™ to facilitate its degradation by the lysosome. Under hypoxic conditions, Vasorin expression is high. Vasorin binds to and stabilizes membranous Notch1 to permit ligand binding, followed by proteolytic cleavage to release the NICD1 and transactivate Notch target genes.

*p < 0.05; **p < 0.01; ***p < 0.001

Data are represented as mean ± SD. See also Figure S7.