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. 2015 Apr 16;2(1):11–18. doi: 10.1016/j.ajur.2015.04.011

Figure 1.

Figure 1

TGF-β signaling pathway in prostate cancer cells. The ligand TGF-β binds to cell transmembrane receptor TGF-βRII (serine threonine kinase), subsequently recruiting TGF-βRI, to form receptor–ligand complex. This process can be promoted by the TGF-βRIII transmembrane receptor. The activated receptor–ligand complex leads to phosphorylation of SMAD2 and SMAD3 in the cytoplasm (receptor activated SMADs) and subsequent formation and nuclear translocation of SMAD2/3 and SMAD4 complex. Once in the nucleus activated Smad4 induces gene transcription for TGF-β target genes regulating proliferation, apoptosis, angiogenesis and EMT. SMAD6/7 negatively regulates R-SMAD activity and nuclear translocation. AR inhibits the TGF-β1/SMAD transcriptional activity, and ultimately TGF-β1-induced growth inhibition and apoptosis. Non-SMAD pathways, including ERK and PI3K/AKT are regulated by TGF-β to promote tumor growth and invasion. In addition, TGF-β promotes tumor growth and metastasis by VEGF-regulated angiogenesis and MMP-9-induced cell invasion. Cofilin coordinates responses to TGF-β required for migratory, invasive and metastatic properties. P, phosphorylation.