Fig. 7: Heterogeneity of ER⁺ primary tumor cells and lung DTCs.

a, b UMAP plots representing FACS-sorted MCF-7:RFP⁺ cells isolated from primary tumors (a) and lungs (b). Colors code for different cell clusters. c Violin plot showing “HALLMARK_EMT” gene set enrichment score in cell clusters of the primary tumors. Boxplots inside each violin describe the interquartile range, bold dots indicate median. Boxplot whiskers show minimum and maximum values. Statistical significance was assessed by fitting a generalized linear mixed model and computing the estimated marginal means across all the identified cell clusters. Tukey’s method was used to assess adjusted p-values. d Integrated UMAP plot showing MCF-7:RFP cells isolated from primary tumors (grey) and lung tissues (color-coded according to clusters from b). e–g UMAP plots representing levels of selected transcripts in primary MCF-7:RFP (e) and lung DTCs (f, g). Numbers describe centroid of clusters identified in Fig. 7a and b. Violet gradient represents low, yellow gradient high gene expression. h Ridge plot showing normalize enrichment scores (NES) in the active versus dormant clusters identified in lung DTCs for the “IL6_JAK_STAT3_SIGNALING” and “TNFA_SIGNALING_VIA_NFKB” hallmark gene sets. Statistical significance was assessed by Welch’s t-test. i UCSC genome browser screenshot showing IL6-induced pSTAT3 binding at CDH1 promoter and enhancer regions. The browser window shows regions, highlighted in yellow, which are bound by phosphorylated STAT3 upon IL6 stimulation in MCF-7 and T47D cells³⁶. *, **, ***, ****, and n.s represent P < 0.05, 0.01, 0.001, 0.0001, and not significant, respectively.