The growth factor TGFbeta (transforming growth factor beta) was initially characterized as a repressor of cellular proliferation. However, studies over the last few years have highlighted another striking property of TGFbeta, which is its capacity to enhance development of the extracellular matrix and formation of metastases from primary tumors. Our understanding of TGFbeta signaling mechanisms has advanced substantially with the identification of the SMAD proteins that transduce TGFbeta signals from the cell membrane to the nucleus where they regulate transcription. Activation of these inducible SMADs occurs through a series of serine phosphorylations mediated by TGFbeta receptors. Other members of the SMAD family act antagonistically downstream of TGFbeta and participate in feedback regulation loops. The fact that members of the TGFbeta family are involved in biological processes as diverse as development, cell proliferation and the immune response can be explained by the intricate regulation of TGFbeta signaling, which involves tissue specificity as well as synergy with distinct signaling pathways. The dual role of TGFbeta as regulator of cellular proliferation and metastasis inducer opens novel possibilities for the use of TGFbeta signaling as a target for cancer therapy.
[Cellular signaling in response to TGFbeta: the paradox of a factor that blocks cell proliferation and enhances metastasis]
Vignais, M. L.
1999-11 / vol 86 / pages 903-10
Phosphorylation; Ligands; Neoplasm Invasiveness; Signal Transduction/*physiology; Extracellular Matrix/physiology; Trans-Activators/metabolism; Transforming Growth Factor beta/*physiology; Cell Division/*physiology; DNA-Binding Proteins/metabolism; Neoplasm Metastasis/*physiopathology; Receptors, Transforming Growth Factor beta/metabolism