TGF- signaling: A complex role in tumorigenesis

Tumor progression can be affected by various cellular components of tumor cells and/or by tumor microenvironmental factors. The tumor microenvironment comprises a variety of nonmalignant stromal cells and inflammatory cytokines, which are pivotal in tumor promotion and progression. The transforming growth factor- (TGF-) ligands (TGF-1, 2 and 3) are secreted inflammatory cytokines, which are known to be involved in various aspects of tumor development through two transmembrane serine-threonine kinase receptors, TGFR1 and TGFR2. TGF- promotes or inhibits tumorigenesis depending on the concurrent gene mutations and tissue microenvironment present through the small mothers against decapentaplegic (Smad) and non-Smad pathways. This review aims to provide a comprehensive overview of the role of the TGF- pathway in tumor initiation and progression.