TGF-β Signaling

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. Click here to open a larger version of this image in a new window.

Downstream Pathways

Cell Cycle Control

Diseases in Which Pathway is Aberrantly Activated

Colorectal cancer
Glioblastoma multiforme
Pancreatic cancer

Therapies That Target This Pathway

TGFBR1 inhibitors

Genes Involved in the Pathway

Last Updated: May 24, 2016

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