Fig. 4: EGF–SOX9–FN1 axis promotes tumour survival.
From: Precancerous niche remodelling dictates nascent tumour persistence
a, Cartoon showing the composition of a tumour cell. b, The cell–cell communication network. Circles represent cells; circle sizes show cell numbers; and the thickness of the connections represents the number of significant interactions. c, Heatmap showing the top 10 signalling predictions. Interactions in Tumour (Tmr) 12 keratinocytes and Tmr fibroblasts are highlighted in yellow. Signals with the strongest interactions in Tmr fibroblasts are highlighted in pink; in Tmr 12, keratinocytes are highlighted in cyan. d, Top: schematics of the chemoattractant assay. Bottom: representative images. Scale bars, 25 µm; inset, 10 µm. FBS, fetal bovine serum. e, Percentage of fibroblasts crossing the membrane. Data are expressed as mean ± s.e.m. Dots represent replicate cultures from n = 4 mice. Significance assessed by one-way Welch’s ANOVA with multiple comparisons (other groups in EDF 10c). f, Schematic representation of epithelioid and fibroblast co-culture treated with gefitinib (GFT) or vehicle (DMSO). g, Representative images from f showing fibroblast interaction with keratinocytes in DMSO and EGFR inhibition (GFT) conditions. Top insets show PDGFRα+ fibroblast (red) heterogeneity: PDGFRαlow fibroblasts assemble adjacent to keratinocytes, whereas PDGFRαhigh fibroblasts position further away in controls. Fibroblast activation at the border is labelled by VIM (white) and FN1 (green). This was inhibited in GFT (bottom). Green, CDH1; nT, nuclear Tomato; KRT, keratinocytes, red; blue, DAPI. Scale bars: main, 500 µm; insets, 50 µm. h, Schematic representation of keratinocyte–fibroblast interactions under DMSO and GFT conditions. i, Experimental protocol of drug intervention with a fibronectin assembly-inhibiting peptide (FUD) or GFT 20-day regimen with the DEN treatment. j, Tumour burden decreased in the GFT and FUD groups compared with vehicle (VHC) or scrambled (SCR) control, respectively. Tissues were collected 10 days after DEN treatment. Data are from n = 3 (VHC), n = 4 (GFT), n = 5 (SCR) or n = 5 (FUD) mice. Data represent mean ± s.e.m. Significance was assessed by one-tailed Mann–Whitney test. Images were captured by confocal microscopy. Illustrations in a, d, f, h and i were created in BioRender; Alcolea, M. https://BioRender.com/eghet5p (2026).
