TGF-β: Duality of Function Between Tumor Prevention and Carcinogenesis

• Published in: JNCI : Journal of the National Cancer Institute Vol. 106; no. 2; p. djt369
• Main Authors: PRINCIPE, Daniel R, DOLL, Jennifer A, BAUER, Jessica, JUNG, Barbara, MUNSHI, Hidayatullah G, BARTHOLIN, Laurent, PASCHE, Boris, CHUNG LEE, GRIPPO, Paul J
• Format: Journal Article
• Language: English
• Published: Cary, NC Oxford University Press 01.02.2014
• Subjects: Animals; Anticarcinogenic Agents - metabolism; Anticarcinogenic Agents - pharmacology; Apoptosis; Biological and medical sciences; Cadherins - metabolism; Carcinogenesis - metabolism; Carcinogens - metabolism; Carcinogens - pharmacology; Cell Proliferation; Cell Transformation, Neoplastic - chemically induced; Cell Transformation, Neoplastic - metabolism; Disease Progression; Humans; Medical sciences; Neoplasms - chemically induced; Neoplasms - metabolism; Neoplasms - prevention & control; Neovascularization, Pathologic - chemically induced; Neovascularization, Pathologic - prevention & control; Protein-Serine-Threonine Kinases - metabolism; Receptors, Transforming Growth Factor beta - metabolism; Review; Signal Transduction; Transforming Growth Factor beta - metabolism; Tumors; Up-Regulation; Prevention; Tumor; Cancerology; Transforming growth factor β; Carcinogenesis
• ISSN: 0027-8874; 1460-2105
• DOI: 10.1093/jnci/djt369

Several mechanisms underlying tumor progression have remained elusive, particularly in relation to transforming growth factor beta (TGF-β). Although TGF-β initially inhibits epithelial growth, it appears to promote the progression of advanced tumors. Defects in normal TGF-β pathways partially explain this paradox, which can lead to a cascade of downstream events that drive multiple oncogenic pathways, manifesting as several key features of tumorigenesis (uncontrolled proliferation, loss of apoptosis, epithelial-to-mesenchymal transition, sustained angiogenesis, evasion of immune surveillance, and metastasis). Understanding the mechanisms of TGF-β dysregulation will likely reveal novel points of convergence between TGF-β and other pathways that can be specifically targeted for therapy.