TGFB1 and neoplasm: TGF-β signaling activates TGFBR1 via TGFBR2, leading to R-SMADs forming a complex with SMAD4 to regulate genes involved in cell cycle arrest and apoptosis.308 In the early stages of cancer, TGF-β signaling exerts a tumor-suppressive effect by inducing growth arrest and apoptosis in epithelial cells.