Fig. 5: SHH pathway is important for malignant transformation in a subset of MPNSTs and a therapeutic target.

a Capillary-based immunoassay (WES) confirming knockout of PTCH1 and subsequent increased GLI1 activity in HSC1-λ cells. b Trypan blue counts of parental HSC1-λ and PTCH1-knockout clone. Error bars, s.e.m.; n = 3 biologically independent experiments. c PTCH1-knockout in HSC1-λ cell lines leads to upregulation of SHH pathway (GLI1, GLI2 and SMO). Error bars, s.e.m.; n = 3 biologically independent experiments. d Protein blot confirming knockout of PTCH1 in ipNF06.2A cells. e Trypan blue counts of a parental ipNF06.2A cells and PTCH1-knockout clone. Error bars, s.e.m; n = 3 biologically independent experiments. f PTCH1-knockout in ipNF06.2A leads to upregulation of SHH pathway (GLI1, GLI2 and SMO). Error bars, s.e.m; n = 3 biologically independent experiments. g Representative images and quantitative cell migration in HSC1-λ cell lines. Error bars, s.e.m; n = 8 biologically independent experiments. h Representative images and quantitative colony formation in HSC1-λ cell lines. Error bars, s.e.m; n = 8 biologically independent experiments. i Representative images and quantitative colony formation in ipNF06.2A cells. Error bars, s.e.m; n = 3 biologically independent experiments. j 4 MPNST cells lines were screened for SHH pathway activation. Error bars, s.e.m; n = 3 biologically independent experiments. k IC50 curves of S462TY and STS-26T cells treated with sonidegib. Error bars, s.e.m; n = 3 biologically independent experiments. l Survival curves of mouse xenografts of S462TY and STS-26T treated with sonidegib at a dose of 20 mg/kg/day or vehicle starting day 14. Median survival for S462TY-Sonidegib vs S462TY-Vehicle (78 vs 45 days, log-rank test, p = 0.03). Source data provided as source data file.