Extended Data Fig. 3: JAK–STAT signaling is specifically required for AR therapy resistance.
a, Relative expression of JAK–STAT genes in LNCaP/AR-sgTP53/RB1 cells transduced with Cas9 and annotated guide RNAs. p-values were calculated using two-tailed multiple t-test with Welch’s correction. b, Western blot of JAK1-3 and STAT1-3 proteins in LNCaP/AR cells transduced with Cas9 and annotated guide RNAs; representative pictures of 2 repeats with similar results were shown. c, Relative cell number of LNCaP/AR cells transduced with annotated CRISPR guide RNAs. Cells were treated with 10 µM enzalutamide (Enz) for 8 days, and cell numbers (viability) were measured using CellTiter-Glo assay, all normalized to sgTP53/RB1 group. p-values were calculated using one-way ANOVA with Bonferroni multiple-comparison test. d, Relative cell number of CWR22Pc cells transduced with annotated shRNAs. e, Relative cell number of CWR22Pc cells transduced with annotated shRNAs and/or Cas9 and CRISPR guide RNAs. For panel d-e, cell numbers were measured by cell proliferation assay, normalized to Veh condition, and p-values were calculated using two-way ANOVA with Bonferroni multiple-comparison. f, Relative cell number of LNCaP/AR-sgNT cells transduced with Cas9 annotated CRISPR guide RNAs. Cells were treated with 10 µM enzalutamide (Enz) for 8 days and cell number was measured using CellTiter-Glo assay, all normalized to sgNT group. p-values were calculated using one-way ANOVA with Bonferroni multiple-comparison test. g, Relative cell number of LNCaP/AR-sgTP53/RB1 cells transduced with Cas9 annotated CRISPR guide RNAs. Cells were treated with DMSO for 8 days and cell number was measured using CellTiter-Glo assay, all normalized to sgTP53/RB1 group. p-values were calculated using one-way ANOVA with Bonferroni multiple-comparison test. For all panels unless otherwise noted, n = 3 independently treated cell cultures and mean ± s.e.m. is represented. p-values were annotated in figures.
