The transforming growth factor-β (TGFB1) cell signaling pathway plays a complex role in cancer development, progression, and metastasis. SMADs function in cell signal transduction from TGFB1 ligands to activate gene transcription. The TGFB1 signaling pathway may be activated by a TGFB1 dimer binding to the TGFBR2 receptor. 
Figure 1. Binding of the TGFB1 ligand dimer to the TGF-beta receptor type-2 (TGFBR2) promotes dimerization of TGFBR2 with TGFBR1 and results in transphosphorylation of TGFBR1. The activated TGF-beta receptor type-1 activates R-SMADs (SMAD2 and SMAD3) via phosphorylation. SMAD2 and SMAD3 trimerize with a co-SMAD (SMAD4). The SMAD trimer enters the nucleus to activate gene transcription and promote cell growth and survival. Specific nodes in the pathway that are therapeutically actionable are noted.