Extended Data Fig. 9: Repurposing clinically approved inhibitors targeting β-catenin degradation.
(a) Drug responses (AUC) to the GSK3β-inhibitor (CHIR99021) were plotted for lymphoid (n = 98 cell lines, biological replicates) and solid (n = 298 cell lines, biological replicates) tumors (CTD2 screen). Data are represented as mean±s.d and two-sided unpaired t-test was used to calculate significance. (b) To assess whether LY2090314 induced any changes in epithelial tissues, histopathological evaluation was performed in colon, lung, liver and kidneys of the mice that received vehicle control or LY2090314 (n = 4 biological replicates/group) and representative images of H&E staining are shown. (c) To characterize phenotypic changes induced by LY2090314 treatment, B-ALL cells harvested from LY2090314 (red, n = 9 mice, biological replicates), or vehicle (green, n = 10 mice, biological replicates) treated mice were analyzed by FACS for surface expression of CD20, CD19, CD10, CD34, IL7R, TSLPR, VPREB1 and CD117. Fold-changes in mean fluorescence intensities (MFI [FC], y-axis) following LY2090314 treatment compared vehicle control are shown. No major differences were observed (two-sided unpaired t-test). Data are presented as mean±s.d.
