Fig. 7: Compound screening identifies GCN5/PCAF as a therapeutic target for eliminating CSCs.

a Schematic depiction of the screening process that identified GCN5/PCAF inhibitors as effective reducers of CSCs. b Chemical structures of GCN5 inhibitor GSK4027 and its negative control GSK4028, and L-Moses with its corresponding negative inhibitor D-Moses. c Dot plots of CSC markers in DMSO, GSK4027 and L-Moses treated samples. d Immunoprecipitation of E2F1 shows its binding to pRb and GCN5. e Immunoprecipitation of E2F4 shows its binding to pRb, RBL2 and GCN5. f–h GCN5 inhibition reduces the self-renewal of CSCs and sphere size increase assessed by tumour sphere assays. h Representative images of spheres in each condition. i GCN5 KD reduces the self-renewal capacity of CSCs in three PDAC cell lines. j E2F1 KD and E2F4 KD reduce GCN5 binding to WNT loci analysed by ChIP-qPCR in CSCs. k GCN5 binding to WNT loci and its binding is reduced by pRb and RBL2 as analysed by ChIP-qPCR in CSCs. l GCN5 mediates H3K9ac on WNT loci and this is reduced by pRb and RBL2. m Schematic depiction of using primary tumour sample from PDAC patients. n–p GCN5 inhibition reduces double and triple CSC marker positive CSCs from primary tumour sample from PDAC patients. q The abundance of CSCs is decreased by GCN5 inhibitors in primary tumours from patients. Data are presented as mean values ± SD. Graphs depicted in (f, g, i, j, k, l, q) are n = 3 independent experiments. Statistical analysis in (f, g, i, j, k, l, q) was performed by 2-way ANOVA with multiple comparisons with Tukey correction. Source data are provided as a Source Data file.