Through the integration of multi-omics data, functional experiments, and clinical analyses, this study systematically unveils the molecular mechanism by which CAF-derived FN1 promotes pancreatic cancer metastasis via the integrin-PI3K/AKT axis and elucidates, for the first time, its interaction with an immunosuppressive microenvironment. This evidence concerns the gene AKT1 and familial pancreatic carcinoma.