[TGFbeta, activin and SMAD signalling in thyroid cancer].
TGFbeta and activin are members of the TGFbeta superfamily and play a wide role in development, proliferation and apoptosis. These growth factors exert their biological effects by binding to the type I and II membrane receptors to transduce their signalling through the nucleus by phosphorylation of R-SMADs (SMAD 2/3) and co-SMADs (Smad 4). The proper control of TGFbeta/activin pathway is negatively regulated by inhibitory SMAD (SMAD7) and by E3 ubiquitination enzymes (Smurfs). Physiologically, TGFbeta and activin act as potent growth inhibitors in thyroid follicular cell. Thus, alterations in the receptors and components of SMAD signalling pathway are associated with several types of tumors. Since TGFbeta and activin generate their intracellular signalling through the same components of the SMAD pathway, the unbalance of this pathway impairs both of anti-mitogenic signals in the cell. This review addresses aspects of the molecular mechanisms in the understanding of resistance to the growth inhibitory effects of TGFbeta and activin due to the disequilibrium in the SMAD inhibitory pathway in thyroid neoplasia.
Kimura
Edna T
ET
Departamento de Biologia Celular e do Desenvolvimento, Instituto de Ciências Biomédicas, Universidade de São Paulo, SP, Brazil. etkimura@usp.br
Matsuo
Sílvia E
SE
Ricarte-Filho
Júlio Cézar
JC
D028341:Activins / Q000378:metabolism*; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D017978:Receptors, Growth Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D051785:Smad Proteins / Q000378:metabolism*; D051906:Smad7 Protein; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases
D004268:DNA-Binding Proteins; D017978:Receptors, Growth Factor; C497806:SMAD7 protein, human; D051785:Smad Proteins; D051906:Smad7 Protein; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D028341:Activins; C471641:SMURF2 protein, human; D044767:Ubiquitin-Protein Ligases; D020928:Mitogen-Activated Protein Kinases