[Cellular signaling in response to TGFbeta: the paradox of a factor that blocks cell proliferation and enhances metastasis].
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.
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IGMM/CNRS UMR 5535, 1919, route de Mende, 34293 Montpellier Cedex 5.
D002455:Cell Division / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D005109:Extracellular Matrix / Q000502:physiology; D008024:Ligands; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis / Q000503:physiopathology*; D010766:Phosphorylation; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000502:physiology*
D004268:DNA-Binding Proteins; D008024:Ligands; D018125:Receptors, Transforming Growth Factor beta; D015534:Trans-Activators; D016212:Transforming Growth Factor beta
Signalisation cellulaire en réponse au TGFbeta: le paradoxe d'une cytokine à la fois inhibitrice de la prolifération cellulaire et inductrice de métastases.