Mutation of Lysines 113 and 159 into arginine residues, thus leading to loss of SUMOylation, was reported to enhance Smad4-induced TGFβ-induced transcriptional responses in human breast and colon cancer cells, as well as in developing Xenopus embryo cells suggesting that SUMOylation counteracts Smad4’s ability to mediate TGFβ signaling [50,52]. This evidence concerns the gene TGFB1 and colonic neoplasm.