Cancer-associated fibroblasts promote esophageal carcinogenesis and lung metastasis by CDH11-mediated extracellular matrix environment remodeling

Lung metastasis is a major cause of death in patients with esophageal squamous cell carcinoma (ESCC) and its tumor microenvironment (TME) is highly complex; however, the molecular mechanisms of ESCC lung metastasis are unclear. In this study, the first comprehensive single-cell atlas of ESCC lung metastasis is established using single-cell RNA sequencing of 11 patient samples. The findings highlight the dynamic evolutionary patterns of the TME and distinct characteristics of key cellular subpopulations. The immune microenvironment exhibited significant alterations, with a subpopulation of pro-carcinogenic cancer-associated fibroblasts (CAFs) in primary ESCC foci and lung metastases.