Fig. 1: Tissue fluidification induces a CytoDR gene signature.
From: Tissue fluidification promotes a cGAS–STING cytosolic DNA response in invasive breast cancer
a, Volcano plot of differentially expressed genes (DEG) in control and RAB5A-expressing MCF10.DCIS monolayers. All significantly RAB5A-expressing deregulated genes are in red (upregulated) and blue (downregulated). Enrichment (log2(fold change)) is plotted on the x-axis and significance (Wald test –log10(p-value two-sided)) is plotted on the y-axis. Labels are the most upregulated genes. Outlined in red are interferon-stimulated genes. b, GSEA of DEGs in RAB5A-expressing MCF10.DCIS.com monolayer over control cells. GSEA was performed using the Hallmarks pathway gene sets in the GSEA Molecular Signatures Database. Moderated t-statistic was used to rank the genes. Significantly enriched pathways are reported (one-sided P < 0.05) with the bar outline colour corresponding to the BH-adjusted P value. P values were calculated as the number of random genes with the same or more extreme enrichment score (ES) value divided by the total number of generated gene sets. c, GSEA enrichment plot of differentially expressed genes in RAB5A-expressing MCF10.DCIS.com monolayer using the KEGG (Kyoto Encyclopedia of Genes and Genomes) cytosolic DNA-sensing pathway (hsa04623). The green curve corresponds to the ES curve, which is the running sum of the weighted ES obtained from GSEA software, while the normalized ES (NES) and the corresponding one-sided P value are reported within the graph. d, Scatter plots of mRNA expression levels of IFI27, IFI44, IFI44L, IFI6, IFIT1, IFIT3, ISG15, MX2 and OASL determined by qRT-PCR in RAB5A-expressing MCF10.DCIS monolayers relative to control cells. Data are expressed as log10 values, horizontal lines represent group medians. Each dot represents an independent experiment. Values were normalized to the controls of each experiment. e, Immunoblots of lysates from control (CTR) and RAB5A-expressing (RAB5A) MCF10.DCIS.com monolayers with the indicated antibodies (n = 3 independent experiments). Mw is indicated on the left.
