Extended Data Fig. 9. Dasatinib treatment inhibits cell migration and tumor metastasis.
a, The schematic diagram shows that SMARCD3 induces PC radial migration and MB metastasis mediated by the Reelin/DAB1-activated SFK loop. b, IHC and quantitative analysis of expression levels of p-Src (416) and total Src in the tumors derived from mice bearing MED8A and D458 with SMARCD3 KO (n = 8) vs WT (n = 10), respectively. Boxed regions correspond to the regions shown in Fig. 7e. c, d, Representative images showing cell migration of MED8A (n ≥ 5) and D458 (n ≥ 7) cells treated with DMSO or indicated concentrations of dasatinib by Transwell assay. e, Scheme of experiment in which mice bearing MB were gavaged with placebo, low dose, and standard dose dasatinib. f, Bioluminescence images and pie charts showing mice bearing D458 cells with dasatinib treatment at day 21 after intracranial implantation. g, IHC quantitative analysis of Ki67 levels in the treated mice (n = 7 for each group). h, The schematic diagram shows that SMARCD3 plays a central role in cerebellar development and MB metastatic dissemination by regulating the Reelin/DAB1/Src signaling at the molecular, cellular, and tissue/organ levels. SMARCD3 transcription regulation is mediated by chromatin hubs during cerebellar development and MB aggressiveness. Targeting SMARCD3/Reelin/DAB1/Src signaling provides a potential novel antimetastatic therapy for patients with MB. n represents the number of the biologically independent samples from at least 3 independent experiments (c, d) or mouse samples (b, g); data are presented as the mean ± s.d. P value was calculated using two-tailed unpaired t-test (b), or one-way ANOVA with Dunnett’s multiple comparison test (c, d, g). NS, not significant, ∗∗∗∗P < 0.0001.