NR2F2 in cancer-associated fibroblasts drives immune microenvironment remodeling and promotes lung adenocarcinoma progression

Background: The high heterogeneity of lung adenocarcinoma (LUAD) is largely due to its complex tumor immune microenvironment (TIME). Cancer-associated fibroblasts (CAFs) are a core matrix component of TIME. However, their functional heterogeneity and the specific molecular mechanisms driving tumor progression have not been fully elucidated. In addition, the role of nuclear receptor NR2F2 in tumor development is still controversial. Method: experiments and validated the biological role of NR2F2 through a coculture system. Functional validation was conducted through siRNA knockdown, plasmid overexpression, CCK-8 assay, EdU labeling, and Transwell experiments. Result: functional experiments, overexpression of NR2F2 in CAFs enhanced tumor cell proliferation and invasion, whereas knockdown of NR2F2 attenuated these malignant phenotypes. Conclusion: experiments. NR2F2 promotes malignant remodeling of TIME by synergistically enhancing TGF-β signaling and EMT processes. Our study provides not only a solid theoretical foundation but also a therapeutic target to explore new therapeutic options targeting the CAFs-TGF-β-EMT axis.