Single-cell and spatial transcriptomics reveal SPRR2A+ epithelial-MMP1+ fibroblast interactions as key drivers of Esophageal Squamous Cell Carcinoma progression

fibroblasts exhibited pronounced spatial co-localization, which may imply reciprocal signaling via TGFB1 and IL6, contributing to the observed extracellular matrix remodeling and malignant behavior. Moreover, functional experiments confirmed that SPRR2A promotes ESCC cell migration and invasion. Altogether, our study characterizes a coordinated epithelial-fibroblast corsstalk and a defined fibroblast differentiation hierarchy, offering new mechanistic insights into the ESCC pro-tumorigenic niche.