Fig. 1: Ectopic expression of β-catenin in treatment-refractory MBs reduces self-renewal gene expression and tumor burden while increasing overall survival.
From: Wnt activation as a therapeutic strategy in medulloblastoma
a Multivariate survival analysis including index, age, metastatic status, and subgroup shows significant association with patient survival using the Bmi1 (p = 0.0004774) and Sox2 (p = 0.001193) signatures. b Bmi1 and Sox2 protein levels are significantly reduced in Group 3 (HD-MB03, D425) MB lines when compared with Wnt MB (BT853) (n = 3, independent experiments per MB line, 1 line per subgroup). Differential Axin2 (Group 3: p = 0.0014, Group 4: p = 0.0011), Bmi1 (Group 3: p = 0.0018, Group 4: p = 0.000087), and Sox2 (Group 3: p = 0.0011, Group 4: p = 0012) transcript levels following β-catenin overexpression in (c) Group 3 and (d) Group 4 MB lines (n = 3, independent experiments per MB line, 1 line per subgroup, all samples normalized to GAPDH). e Tumor sphere formation is impaired following β-catenin overexpression in Group 3 (p = 0.0005) and Group 4 MBs (p = 0.0058) (n = 3, independent experiments per MB line, 1 line per subgroup). f Representative histology images showing significant reduction in tumor formation in xenografts generated from Group 3 β-catenin-overexpressing lines (n = 5) compared with control (n = 5). g β-catenin overexpression xenografts (n = 5, median survival 32.0 days) display a significant increase in overall survival when compared with control xenografts (n = 5, median survival 22.0 days) (p = 0.0043). Histology image scale bar = 5000 μm. Panels (c–e) contain error bars expressed as mean ± standard error (mean) using two-tailed, unpaired Student’s t test. Panel (g) analyzed using log-rank (Mantel–Cox) test. ****p < 0.0001.
