Transforming growth factor-beta and malignant melanoma: molecular mechanisms.
Transforming growth factor family members (TGF-beta) are secretory polypeptides that have dual tumor-suppressor and oncogenic effects. They signal through kinase receptor complexes on the cell surface, which phosphorylate cytoplasmic mediators (SMADs). Upon phosphorylation, SMADs march to the nucleus and interact with coactivators or corepressors to mediate the transcriptional regulation of several genes resulting in diverse effects. In tumorigenesis, malignant cells escape from the tumor-suppressive effects of TGF-beta by mutational inactivation or dysregulated expression of the molecular components in TGF-beta signaling pathway. Although melanoma cells are resistant to the tumor-suppressive effects of TGF-beta, there are no detectable defects at the receptor/SMAD level. Therefore, in these lesions, it is possible that TGF-beta effects occur independently of TGF-beta receptor/SMAD pathway. This review seeks to examine the present knowledge about TGF-beta receptor/SMAD signaling pathway and its related genes (SMADs, SKI, Filamin, endoglin, Follistatin, and other molecules) in melanomas.
Hussein
Mahmoud R
MR
Department of Pathology, School of Medicine, Assuit University, Assuit, Egypt. mrh17@swissinfo.org
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D008545:Melanoma / Q000378:metabolism*; D020239:Receptor Cross-Talk / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D051785:Smad Proteins; D015534:Trans-Activators / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D004268:DNA-Binding Proteins; D051785:Smad Proteins; D015534:Trans-Activators; D016212:Transforming Growth Factor beta