Fig. 5: Crosstalk between AR inhibition and β-catenin activaiton.

A TCF reporter activity (left panels) and expression of AXIN2, RNF43, ZNRF3, and NKD1 evaluated by RT-qPCR (right panels) on C42B and LNCaP cells expressing or not β-catenin WT or mutant variants D32G or T41A under DMSO (vehicle) or enzalutamide treatment (30 µM, 24 H). Statistical significance for TCF reporter activity was assessed by two-way ANOVA and Šídák’s multiple comparisons test. Statistical significance for gene expression analysis was assessed by t test. B I. Schematic representation of PDX-derived organoid drug testing experimental design. II. CellTiter-Glo® 3D Cell Viability Assay of organoids derived from MDA PCa 173-2 or 183-A treated with enzalutamide (0–200 µM; 72 H; DMSO as vehicle). Statistical significance assessed by non-linear regression comparison. C I. Schematic representation of in vivo castration experimental design. II. MDA PCa 173-2 tumor volume curves over time for each mouse in each experimental group. D Serum PSA levels measured at endpoint, from mice in each group on castration experiment. E Expression of AXIN2, RNF43, ZNRF3, and NKD1 evaluated by RT-qPCR on 173-2 tumors from each experimental group. Statistical significance assessed by one-way ANOVA. F Evaluation of the Wnt signature genes on paired patient samples pre and post enzalutamide treatment. I. AXIN2, RNF43, ZNRF3, and NKD1 expression before and after treatment. II. Principal component analysis based on AXIN2, RNF43, ZNRF3, and NKD1 expression levels. Cases harboring a CTNNB1 driver mutation are depicted in red. WT: wild type; Mut: mutant. Statistical significance: * P < 0.05; ** P < 0.01; *** P < 0.001.