For the first time in this study, it was revealed that SMAD4, a major regulator of TGF-β signaling preceding cancer EMT and metastasis in advanced cancers, was a target for O-GlcNAcylation (Fig. 3) and that O-phosphorylation is interrupted during hyper-O-GlcNAcylation caused by OGT overexpression (Fig. 2F). This evidence concerns the gene OGT and cancer.