A, Strong nuclear expression of PYGO2 in two PDX models of CRPC, detected by IHC. Scale bar, 100μm. B, Reduction of PYGO2 level in two PDX models by PYGO2-targeting siRNA, detected by western blot. C, PYGO2-targeting siRNA (Sigma-Aldrich, SASI_HS01_00059018) impaired PDX tumor growth. Arrows indicate the start day for intratumoral siRNA infusion. D, Luciferase assay measuring effect of PYGO2 knockdown in PC3 on the response to Wnt-3A-mediated TOPFlash reporter activity. E, Effect of PYGO2 knockdown in PC3 on the expression of indicated proteins, detected by western blot. F, GSEA analysis for transcriptomic samples. Samples from Grasso et al. (4), dichotomized by normalized expression level of the PYGO2 probe A_23_P411953. KEGG Wnt pathway with 138 genes was the gene set for the analysis. Localized PCa and CRPC samples were analyzed separately, with FDR q-value being 0.051 and 0.070, respectively. Both FDR q-values are <0.25, the recommended FDR cutoff value by the GSEA User Guide.