PS 19. Vicious cycle in TGF-β signaling in tumor progression

Historically, the underlying mechanism promoting tumor progression has been elusive. Recent evidence demonstrates that many tumors harbor a defect in the negative feedback loop regulating sensitivity to and expression of transforming growth factor-β (TGF-β) This deregulation creates a unique TGF-β mediated tumor microenvironment that sets off a cascade of downstream events. These events activate multiple oncogenic pathways, precipitating in a vicious cycle that promotes many of the hallmarks of tumorigenesis, including sustained angiogenesis, immune system evasion, proliferation, loss of apoptotic response, epithelial to mesenchymal transition and metastasis. These combined effects lead to uncontrolled tumor progression and lethal disease. Uncovering mechanisms of TGF-β dysregulation in tumors will reveal novel points of convergence between TGF-β and other pathways which may be targeted with new therapeutic approaches.