SMAD2 and colorectal carcinoma: In CRC, D4R interacts with transforming growth factor β receptors (TGFBR1 and TGFBR2), activating the phosphorylation of Smad2 and promoting the nuclear translocation of the Smad2/Smad4 complex, which transcriptionally upregulates SNAI1 and JAG1, inducing EMT and enhancing metastasis [407].