Taken together, our data suggest that invasive Fn activates β-catenin signaling via a TLR4/P-PAK1/P-β-catenin S675 cascade in the carcinogenesis of CRC; TLR4 and PAK1 could be potential pharmaceutical targets for the treatment of Fn-related CRCs. This evidence concerns the gene FN1 and colorectal carcinoma.