Fig. 5: Early tumour niche remodelling in human oesophageal squamous cell carcinoma.

a, Schematic representation of the tumour sample origin shown in b–d; tumour resections from human patients performed before chemotherapy (chemo-naive). b, Representative confocal image (from n = 4 patients) of a T1B tumour section showing widespread KRT6A (red), and heterogenous SOX9 (cyan) and AREG (magenta) expression; blue, DAPI. The control sample is normal area identified by a pathologist in the tumour section. Scale bar, 200 µm; in insets, 50 µm. c, Representative confocal image (from n = 5 patients) of a T1A tumour section showing widespread KRT17 (yellow), heterogenous SOX9 (cyan) expression and fibroblast attraction to areas marked by PDGFRα (grey) expression. Blue, DAPI. Scale bars, 200 µm; in insets, 10 µm. d, Representative confocal image (from n = 1 patient) of a carcinoma in situ (Tis) whole mount showing heterogenous SOX9 (cyan) expression and fibronectin (FN1, green) accumulation underneath (white arrowhead). Blue, DAPI. Scale bars, 50 µm. e, Schematic representation of the tumour sample origin shown in f; resections were performed after chemotherapy. f, Representative confocal image (from n = 1 patient) of a post-treatment, pathological staging T0 (dysplasia) whole mount, showing heterogenous expression of SOX9 (cyan) and AREG (magenta) and fibronectin (FN1, green) accumulation underneath. Blue, DAPI. The control sample is a biopsy distal to the tumour. Scale bar, 500 µm; in insets, 50 µm. g, Schematic of proposed model whereby epithelial cells respond to genetic perturbation by activating a stress gene signature (tumour 12), denoted by SOX9 and EFG ligand overexpression. This drives the migration of underlying fibroblasts towards the nascent tumour, followed by the formation of a fibrotic scaffold. The establishment of this EGF–SOX9–FN1 signalling axis between epithelial and mesenchymal nascent tumour cells results in the formation of an early tumour niche that favours tumour growth and promotes long-term persistence. Illustrations in a, e and g were created in BioRender; Alcolea, M. https://BioRender.com/e94fdb9 (2026).