The role of TGF-beta in epithelial malignancy and its relevance to the pathogenesis of oral cancer (part II).
The role of transforming growth factor-beta (TGF-beta) in epithelial malignancy is complex, but it is becoming clear that, in the early stages of carcinogenesis, the protein acts as a potent tumor suppressor, while later, TGF-beta can function to advance tumor progression. We review the evidence to show that the pro-oncogenic functions of TGF-beta are associated with (1) a partial loss of response to the ligand, (2) defects of components of the TGF-beta signal transduction pathway, (3) over-expression and/or activation of the latent complex, (4) epithelial-mesenchymal transition, and (5) recruitment of signaling pathways which act in concert with TGF-beta to facilitate the metastatic phenotype. These changes are viewed in the context of what is known about the pathogenesis of oral cancer and whether this knowledge can be translated into the development of new therapeutic modalities.
Prime
S S
SS
Department of Oral and Dental Science, Division of Oral Medicine, Pathology and Microbiology, Bristol Dental Hospital and School, University of Bristol, Lower Maudlin Street, Bristol BS1 2LY, United Kingdom. Stephen.prime@bristol.ac.uk
Davies
M
M
Pring
M
M
Paterson
I C
IC
D000818:Animals; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism*; D009362:Neoplasm Metastasis / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology; D051785:Smad Proteins; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000502:physiology*
D004268:DNA-Binding Proteins; D051785:Smad Proteins; D015534:Trans-Activators; D016212:Transforming Growth Factor beta