Fig. 4
In combination with targeted therapy, CDC7 inhibition induces downregulation of genes involved in pathways associated to NE transformation. a Dotplots showing results for the pathway enrichment analysis on DEGs from combo- versus enzalutamide-treated tumor conditions in the transcriptomic data from TP53/RB1-inactivated 22PC and LnCap/AR xenografts treated in vivo and collected at an intermediate timepoint (day 17). Categorized pathways of interest, previously implicated in NE transformation,1,2 are shown. b Force-directed layouts (FDLs) for single-cell transcriptomic data in tumors collected during a time course experiment from a GEMM prostate NE transformation model (PtRP) described in ref. 12 showing increased NE transformation phenotype over time. FDLs are separated by time point, and cells undergoing NE transformation are labeled according to their trancriptomic profile resembling PRAD or NEPC. c FDLs separated by time point, with cells for each time point colored by CDC7 expression levels. d Dotplot showing the magnitude of CDC7 expression and percentage of CDC7-expressing cells at the different time points of the time course GEMM experiment. e Heatmap of gene trends of select genes of relevance in NE transformation ordered by the putative transition from adenocarcinoma to NEPC, with gene labels colored in the same way the aforementioned groups (scale gene trends of imputed expression, −0.5 to 2.0). The top panel shows a spline fit of the average Z-score for GSEA pathways of interest
