Fig 2: The canonical SWI/SNF complex is the primary cofactor of enhancer-binding transcription factors and is essential for enabling their oncogenic gene programs.(a, c) Genome-wide ChIP-seq read-density heatmaps and Venn diagrams for CTCF in VCaP (a) or LNCaP (c) cells treated with either DMSO or AU-15330 (1 µM) for 6h. Vinculin is the loading control probed on a representative immunoblot. (b, d) Immunoblots of indicated proteins in VCaP (b) or LNCaP (d) cells treated with AU-15330 (1 µM) for increasing time durations. Total histone H3 is the loading control probed on all immunoblots. This experiment was repeated independently twice. (e) GSEA plots for ERG, FOXA1, and MYC-regulated genes using the fold change rank-ordered gene signature from AU-15330-treated (1 nM, 24h) VCaP cells. NES, net enrichment score; adj P, adjusted p-value; DEGs, differentially expressed genes. (f, g) GSEA of FOXA1, MYC, or ARID1A-regulated genes (see Methods for gene sets) in the fold change rank-ordered AU-15330 gene signature in indicated PCa cells. DEGs, differentially expressed genes. (n = 2 biological replicates, GSEA enrichment test) (h, i) Expression of indicated genes (qPCR) in VCaP (h) or LNCaP (i) cells upon treatment with DMSO, AU-15330, dBRD7 (BRD7 degrader), or dBRD7/9 (dual BRD7 and BRD9 degrader) at 1 µM for 24h. Data are presented as mean +/- SD (n = 3, technical replicates) from one-of-two independent experiments. (j) Immunoblots for indicated proteins in LNCaP and VCaP cells treated with AU-15330, dBRD9 (BRD9 degrader), or VZ185 (BRD7/9 degrader) at indicated concentrations. Vinculin is the loading control probed on all immunoblots. This experiment was repeated independently twice. Source data

Fig 3: The SWI/SNF complex is a common chromatin cofactor of the central transcriptional machinery in PCa cells.(a) The overlap between AR, FOXA1, ERG, and SMARCC1 ChIP-seq peaks in VCaP cells. (b) Genomic annotation of oncogenic transcription factor and SWI/SNF (SMARCC1) chromatin binding sites. (c) The overlap between transcription factor and SWI/SNF complex shared genomic sites (from a) and H3K27Ac ChIP-seq peaks along with the genomic annotations of the shared binding sites. (d) Left: volcano plot showing the AR interacting proteins identified from AR immunoprecipitation followed by MS. Significantly enriched SWI/SNF subunits are highlighted in red (two-sided t-test). Right: Overlap between AR, FOXA1, and ERG interacting proteins identified from in-house or publicly available datasets. (e) Immunoblots for indicated proteins followed by nuclear co-immunoprecipitation (IP) of AR, FOXA1, ERG, or SMARCC1 (a core SWI/SNF subunit) in VCaP and LNCaP cells after DHT (dihydrotestosterone) stimulation (10 nM, 3h). This experiment was repeated independently twice. Source data

Fig 4: ETS related gene (ERG) is a key mediator for endothelial cells-induced docetaxel resistance in prostate cancer cells. (A, B) 22Rv1 and C4–2B cells were co-cultured with human umbilical vein endothelial cells (HUVEC) for the indicated days, qPCR and western blot analysis were performed to assess ERG expression. (C) Cell viability of C4–2B cells transfected with ERG and siRNA targeting ERG incubated with the indicated dose of docetaxel for 48h. Western blot was conducted to measure ERG expression. (D, E) The percentage of apoptotic C4–2B and C4-2B-ERG cells treated with 10 nM docetaxel for 48 h. (F) The expression of total/cleaved PARP and caspase-3 in C4–2B and C4-2B-ERG cells treated with docetaxel was determined by western blotting. Data were presented as mean ± SD; **P < 0.01; ***P < 0.001.

Fig 5: ERG silencing in HLMECs cells impairs angiogenesis and enhances the secretion of fibrogenic mediators.a Effect of ERG-siRNA on VEGFA induced in vitro angiogenesis. Representative fields are shown. Quantitative analysis of tube formation was indicated as the total number of junctions and total vessel length. Image analysis in the whole photographed area were performed by using the software AngioTool. N = 3 independent experiments. Values are summarized as mean and SD and analyzed using a two-tailed Student’s t-test. Source data is provided as a Source Data file. Scale bar: 50 µm. b Immunofluorescence staining shows reduction of VE-Cadherin and loss of cellular junctions (arrows) in ERG-silenced HLMECs compared to control cells. A representative image of n = 3 independent experiments is shown. Scale bar: 50 µm. c Quantitative PCR analysis in ERG-silenced HLMECs compared to control cells. N = 3 independent experiments. Values are summarized as mean and SD and analyzed using a two-tailed Student’s t-test. Source data is provided as a Source Data file. d HLMECs were transfected prior to CM collection and transferred to recipient nHLFs. e qPCR analysis of recipient nHLF exposed to ERG-siRNA derived CM compared to cells exposed to control siRNA derived CM (N = 3 independent experiments). Values are summarized as mean and SD and analyzed using a one-way analysis of variance followed by Tukey’s post hoc test. Source data is provided as a Source Data file. f Western blotting analysis of nHLs recipient cells exposed to ERG-siRNA derived CM compared to control siRNA derived CM. N = 1 experiment. g ECM deposition assay in nHLFs exposed to ERG-siRNA derived CM compared to cells exposed to control siRNA derived CM (N = 4 independent experiments, analyzed using two-tailed Student’s t-test). Values are summarized as mean and SD. Source data is provided as a Source Data file. h Workflow employed for the analysis of the secretome in CM collected from control or ERG-silenced HLMECs (created with BioRender.com). i List of secreted proteins from control or ERG-silenced HLMECs ranked by their abundance ratio ERG/control. CM from three independent experiments was pulled and subjected to mass spectrometry. Source data is provided as a Source Data file. *P < 0.05, **P < 0.01, ***P < 0.001.