Extended Data Fig. 7: JAK inhibitor impairs lineage plasticity and restores Enz sensitivity.
a, Enz dose–response curve of LNCaP/AR cells transduced with Cas9 and annotated CRISPR guide RNAs. b, Filg dose–response curve of LNCaP/AR cells transduced with annotated Cas9 and CRISPR guide RNAs. For panel (a-b), p-values were calculated by non-linear regression with two-sided extra sun-of-squares F test. c, Relative cell number of CWR22Pc cells transduced with annotated shRNAs and treated with various treatments, normalized to “Veh” group. Enz denotes 1 μM Enz, Filg denotes 5 μM filgotinib, Enz + Filg denotes the combination of Enz and Filg and Veh denotes DMSO treatment with equal volume as Enz. Cells were treated for 4 days and cell numbers were counted. d, Relative expression of canonical lineage marker genes in CWR22Pc cells transduced with annotated shRNAs and treated with vehicle or Filg, normalized to “shNT + Veh” group. Filg denotes 5 μM filgotinib, and Veh denotes DMSO treatment with equal volume as Filg. e, Cell number of DU145 cells upon treatment administration, measured by cell proliferation assay. f, Cell number of PC3 cells upon treatment administration, measured by cell proliferation assay. For e-f panels, Filg denotes 5 µM Filgotinib and Veh denotes DMSO treatment for 9 days. For all panels unless otherwise noted, n = 3 independently treated cell cultures and mean ± s.e.m. is represented; p-values were calculated using two-way ANOVA with Bonferroni multiple-comparison test and were annotated in figures.
