The TGF-beta signaling, important for a wide range of cellular processes as well as for tumor cell invasion, metastasis, and resistance to chemotherapy (reviewed in Colak and Ten Dijke, 2017), was affected at the level of the intracellular transducer Smad4 (SMAD4) and receptor activated SMADs, namely Smad3 (SMAD3) and Smad5 (SMAD5) and TGF beta (TGFB3) itself. Here, SMAD4 is linked to neoplasm.