Fig. 3: Impact of stress stimuli on epithelial tumor cells within the TME.

a UMAP plot of epithelial tumor cells in NC and MS tumors, grouped by cell subtypes. b Heatmap of the expression levels of the marker genes used for annotation of tumor cell subtypes. c Proportion of each epithelial tumor cell subtype in all tumor cells. Statistical significance was indicated (Fisher’s exact test, **p < 0.01). d Proportion of tumor cells at different stages of the cell cycle. Statistical significance was indicated (Fisher’s exact test, **p < 0.01). Trajectory analysis of epithelial tumor cells, displayed by pseudotime (e) and cell subtype (f). Cell differentiation direction was indicated with red arrows. g Dot plot of Hallmark pathway signature enrichment score in each subtype of epithelial tumor cells. h Volcano plot of DEGs in epithelial tumor cells between MS and NC mice. i GO pathway enrichment analysis of DEGs showing the top 10 pathways (adjusted p < 0.05). j GSEA plot showing representative pathways including epithelial cell proliferation, the cell cycle, and Wnt signaling (MS vs NC). k The signature enrichment score (U score) of representative pathways, including the epithelial cell proliferation, the cell cycle, and Wnt signaling in epithelial tumor cells (MS vs NC). l Ki67 immunofluorescence staining analysis of tumor tissue sections. m Quantification of the Ki67 staining in l (mean ± SEM, n = 5).