SMAD3 and nonpapillary renal cell carcinoma: ,16 The phosphorylation of Smad3 by TβRI was a key initial event in the activation of TGF-β/Smads signaling.17, 18, 19 Despite the importance of the TGF-β-induced EMT, as a regulator of tumor metastasis, the molecular mechanisms underlying EMT in ccRCC have not been completely understood.