Fig. 7: Improved GSC and tumor control with combined Sema3C and Wnt pathway inhibition.
From: Sema3C signaling is an alternative activator of the canonical WNT pathway in glioblastoma
a In vitro extreme limiting dilution assay in shSema3C, shTCF1 or both knockdowns. Tables below show estimated stem cell frequencies in control shNT, shSema3C, shTCF1, and shSema3C + shTCF1 knockdown GSCs (n = 8 technical replicates in each dose, at least three biological replicates, ELDA test, comparing to shSema3C + shTCF1 knockdown GSCs, 387 GSCs: shNT p < 0.0001; shSema3C P = 0.0003; shTCF1 p = 0.0002; 4121 GSCs: shNT p < 0.0001; shSema3C p < 0.0001; shTCF1 p = 0.028). b Western blots of TCF1 and c-Myc in shSema3C knockdown GSCs treated with LGK974 100 μM or vehicle control for 24 h. Western blots were repeated at least twice. c Model of Sema3C regulation of the Wnt pathway in GSCs. Despite upstream Wnt pathway inhibition, Sema3C binds to the Neuropilin 1 (NRP1)—PlexinD1 receptor complex pathway to activate Rac1. Active Rac1 (Rac1-GTP) facilitates β-catenin nuclear translocation to drive Wnt target gene transcription. Source data are provided as a Source data file.
