TGF-β - an excellent servant but a bad master

The transforming growth factor (TGF-beta) family of growth factors controls an immense number of cellular responses and figures prominently in development and homeostasis of most human tissues. Work over the past decades has revealed significant insight into the TGF-beta signal transduction network, such as activation of serine/threonine receptors through ligand binding, activation of SMAD proteins through phosphorylation, regulation of target genes expression in association with DNA-binding partners and regulation of SMAD activity and degradation. Disruption of the TGF-beta pathway has been implicated in many human diseases, including solid and hematopoietic tumors. As a potent inhibitor of cell proliferation, TGF-beta acts as a tumor suppressor; however in tumor cells, TGF-beta looses anti-proliferative response and become an oncogenic factor. This article reviews current understanding of TGF-beta signaling and different mechanisms that lead to its impairment in various solid tumors and hematological malignancies.