Taken together these results suggest that TGFβ1-dependent phosphorylation of 14-3-3σ is a scaffold for tuning of TGFβ cellular response that orchestrates a functional interaction of TGFβ/Smad3 and p53/21 signaling pathways, regulates tumorigenic and radioresistant cancer cell population and can provide a new potential target for anticancer therapy. This evidence concerns the gene SMAD3 and cancer.