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Campo DC | Valor | Lengua/Idioma |
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dc.contributor.author | Matsuzaki, K. | es |
dc.date.accessioned | 2011-06-30T12:02:59Z | - |
dc.date.available | 2011-06-30T12:02:59Z | - |
dc.date.issued | 2006 | - |
dc.identifier.issn | 0213-3911 | es |
dc.identifier.uri | http://hdl.handle.net/10201/22669 | - |
dc.description.abstract | 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. | es |
dc.format | application/pdf | es |
dc.format.extent | 18 | es |
dc.language | eng | es |
dc.publisher | Murcia : F. Hernández | es |
dc.relation.ispartof | Histology and histopathology | es |
dc.rights | info:eu-repo/semantics/openAccess | es |
dc.subject | SMAD | es |
dc.subject | Colorectal cancer | es |
dc.subject.other | CDU::6 - Ciencias aplicadas::61 - Medicina::616 - Patología. Medicina clínica. Oncología | es |
dc.title | Smad3 phosphoisoform-mediated signaling during sporadic human colorectal carcinogenesis | es |
dc.type | info:eu-repo/semantics/article | es |
Aparece en las colecciones: | Vol.21, nº 6 (2006) |
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Smad3 phosphoisoformmediated signaling during sporadic.pdf | 7,34 MB | Adobe PDF | Visualizar/Abrir |
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