It is believed that both cleaved and precursor form of IL-37 could bind with Smad-3 and competitively hindered the formation of Smad-2/Smad-4/Smad-3 tripartite complex, which was responsible for the nuclear translocation of Smad-2 and Smad-4, thus inhibiting the proliferation and invasion of tumor cells in Smad signaling pathway (106). This evidence concerns the gene SMAD4 and neoplasm.