TGF-beta signaling in tumor suppression and cancer progression

Epithelial and hematopoietic cells have a high turnover and their progenito r cells divide continuously, making them prime targets for genetic and epig enetic changes that lead to cell transformation and tumorigenesis. The cons equent changes in cell behavior and responsiveness result not only from gen etic alterations such as activation of oncogenes or inactivation of tumor s uppressor genes, but also from altered production of, or responsiveness to, stimulatory or inhibitory growth and differentiation factors. Among these, transforming growth factor beta (TGF-beta) and its signaling effectors act as key determinants of carcinoma cell behavior. The autocrine and paracrin e effects of TGF-beta on tumor cells and the tumor micro-environment exert both positive and negative influences on cancer development. Accordingly, t he TGF-beta signaling pathway has been considered as both a tumor suppresso r pathway and a promoter of tumor progression and invasion. Here we evaluat e the role of TGF-beta in tumor development and attempt to reconcile the po sitive and negative effects of TGF-beta in carcinogenesis.