Fig. 2. FOXA1 remains a critical lineage transcription factor in NEPC.

a Transcript expression of FOXA family TFs in LuCaPs PDXs (five NEPC and five PRAD; two replicates each). b FOXA1/FOXA2 immunohistochemistry in six representative PDXs. c H3K27ac profiles at FOXA1 in five representative PRAD and NEPC PDXs. d H3K27ac HiChIP loops near FOXA1 in LuCaP 173.1 (NEPC) and LNCaP (PRAD). Bars indicate super-enhancers in five representative LuCaPs of each lineage. Blowups show ChIP-seq read pileups for FOXA1 and ASCL1 in PDXs of the indicated lineage. e, f Proliferation of LNCaP and 42D/42F derivatives with inactivation of FOXA1 by CRISPR (e) or shRNA (f) across two independent experiments (n = 6 replicates). Numbers next to western blots indicate molecular weight markers (kD). g, h Proliferation (g) and expression of neuroendocrine marker proteins (h) with siRNA knock-down of FOXA1 in the NEPC organoid model WCM154. Knock-down was repeated in two independent experiments with similar results. i Essentiality of genes in NCI-H660 (NEPC) versus PRAD cell lines in a published shRNA screening dataset⁷². More negative DEMETER2 scores indicate greater dependency. The blue lines indicate the median DEMETER2 score for pan-essential genes. For all boxplots, box boundaries correspond to 1st and 3rd quartiles; whiskers extend to a maximum of 1.5x the inter-quartile range. Source data are provided as a Source Data file.