Por favor, use este identificador para citar o enlazar este ítem:
http://hdl.handle.net/10201/22669
Twittear
Título: | Smad3 phosphoisoform-mediated signaling during sporadic human colorectal carcinogenesis |
Fecha de publicación: | 2006 |
Editorial: | Murcia : F. Hernández |
ISSN: | 0213-3911 |
Materias relacionadas: | CDU::6 - Ciencias aplicadas::61 - Medicina::616 - Patología. Medicina clínica. Oncología |
Palabras clave: | SMAD Colorectal cancer |
Resumen: | Transforming growth factor-ß (TGF-ß) signaling occurring during human colorectal carcinogenesis involves a shift in TGF-ß function, reducing the cytokine’s antiproliferative effect, while increasing actions that promote invasion and metastasis. TGF-ß signaling involves phosphorylation of Smad3 at serine residues 208 and 213 in the linker region and serine residues 423 and 425 in the C-terminal region. Exogenous TGF-ß activates not only TGF-ß type I receptor (TßRI) but also c-Jun N-terminal kinase (JNK), changing unphosphorylated Smad3 to its phosphoisoforms: C-terminally phosphorylated Smad3 (pSmad3C) and linker phosphorylated Smad3 (pSmad3L). Either pSmad3C or pSmad3L oligomerizes with Smad4, and translocates into nuclei. While the TßRI/pSmad3C pathway inhibits growth of normal epithelial cells in vivo, JNK/pSmad3L-mediated signaling promotes tumor cell invasion and extracellular matrix synthesis by activated mesenchymal cells. Furthermore, hepatocyte growth factor signaling interacts with TGF-ß to activate the JNK/pSmad3L pathway, accelerating nuclear transport of cytoplasmic pSmad3L. This reduces accessibility of unphosphorylated Smad3 to membrane-anchored TßRI, preventing Smad3C phosphorylation, pSmad3Cmediated transcription, and antiproliferative effects of TGF-ß on epithelial cells. As neoplasia progresses from normal colorectal epithelium through adenoma to invasive adenocarcinoma with distant metastasis, nuclear pSmad3L gradually increases while pSmad3C decreases. The shift from TßRI/pSmad3C-mediated to JNK/pSmad3L-mediated signaling is a major mechanism orchestrating a complex transition of TGF-ß signaling during sporadic human colorectal carcinogenesis. This review summarizes the recent understanding of Smad3 phosphoisoform-mediated signaling, particularly “cross-talk” between Smad3 and JNK pathways that cooperatively promote oncogenic activities. Understanding of these actions should help to develop more effective therapy against human colorectal cancer, involving inhibition of JNK/pSmad3L pathway. |
Autor/es principal/es: | Matsuzaki, K. |
Forma parte de: | Histology and histopathology |
URI: | http://hdl.handle.net/10201/22669 |
Tipo de documento: | info:eu-repo/semantics/article |
Número páginas / Extensión: | 18 |
Derechos: | info:eu-repo/semantics/openAccess |
Aparece en las colecciones: | Vol.21, nº 6 (2006) |
Ficheros en este ítem:
Fichero | Descripción | Tamaño | Formato | |
---|---|---|---|---|
Smad3 phosphoisoformmediated signaling during sporadic.pdf | 7,34 MB | Adobe PDF | Visualizar/Abrir |
Los ítems de Digitum están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.