Extended Data Fig. 1: JAK–STAT signaling pathway is enriched in Enz resistant mCRPC with TP53/RB1-deficiency.

a, Heat map represents the significantly changed signaling pathways in LNCaP/AR cell lines transduced with annotated shRNAs and treated with Enz or vehicle, based on GSEA analysis. Signaling pathways specifically enriched in shTP53/RB1 Enz-resistant cells are labeled with red bracket. Three comparations are presented and reads from n = 3 independently treated cell cultures were used for analysis. b, Venn diagram represents the signaling pathways concomitantly altered with TP53/RB1-Loss and SOX2-OE, while also specifically enriched in in shTP53/RB1 Enz-resistant cells. c-g, GSEA analysis of JAK–STAT signaling pathway (KEGG_JAK_STAT_Signaling_Pathway) expression in: (c) SOX2-OE group compared to shNT group; (d) shTP53/RB1 group compared to shNT group; (e) shTP53/RB1 group compared to shTP53/RB1/SOX2 group; (f) shTP53/RB1 + Enz group compared to shNT-Veh group; (g) shTP53/RB1 + Enz group compared to shTP53/RB1 + Veh group. For panel c-g, reads from n = 3 independently treated cell cultures were used for analysis. GSEA p-values were calculated with two-sided permutation test by simulations.