Premium
Transforming growth factor‐β and malignant melanoma: molecular mechanisms
Author(s) -
Hussein Mahmoud R.
Publication year - 2005
Publication title -
journal of cutaneous pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.597
H-Index - 75
eISSN - 1600-0560
pISSN - 0303-6987
DOI - 10.1111/j.0303-6987.2005.00356.x
Subject(s) - smad , r smad , transforming growth factor , cancer research , signal transduction , carcinogenesis , biology , endoglin , acvrl1 , receptor , transforming growth factor beta , melanoma , microbiology and biotechnology , phosphorylation , tgf alpha , endocrinology , cancer , growth factor , genetics , stem cell , cd34
Transforming growth factor family members (TGF‐β) 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‐β by mutational inactivation or dysregulated expression of the molecular components in TGF‐β signaling pathway. Although melanoma cells are resistant to the tumor‐suppressive effects of TGF‐β, there are no detectable defects at the receptor/SMAD level. Therefore, in these lesions, it is possible that TGF‐β effects occur independently of TGF‐β receptor/SMAD pathway. This review seeks to examine the present knowledge about TGF‐β receptor/SMAD signaling pathway and its related genes (SMADs, SKI, Filamin, endoglin, Follistatin, and other molecules) in melanomas.