https://scholars.lib.ntu.edu.tw/handle/123456789/593877
Title: | Matriptase is involved in ErbB-2-induced prostate cancer cell invasion | Authors: | Wu S.-R. Cheng T.-S. Chen W.-C. Shyu H.-Y. Chun-Jung Ko HSIANG-PO HUANG Teng C.-H. Lin C.-H. Johnson M.D. Lin C.-Y. MING-SHYUE LEE |
Issue Date: | 2010 | Publisher: | Elsevier Inc. | Journal Volume: | 177 | Journal Issue: | 6 | Start page/Pages: | 3145-3158 | Source: | American Journal of Pathology | Abstract: | Deregulation of both ErbB-2 signaling and matriptase activity has been associated with human prostate cancer (PCa) progression. In this communication, we investigated the roles of both ErbB-2 signaling in matriptase zymogen activation and matriptase in ErbB-2-induced PCa malignancy. In a human PCa cell progression model, we observed that advanced PCa C-81 LNCaP cells exhibited an aggressive phenotype with increased cell migration and invasion capacity; these cells concurrently showed both enhanced ErbB-2 phosphorylation and increased matriptase zymogen activation compared with parental C-33 LNCaP cells. Moreover, ErbB2 activation, both ligand-dependent (eg, epidermal growth factor treatment) and ligand-independent (eg, overexpression), was able to induce matriptase zymogen activation in this cell line. Inhibition of ErbB-2 activity by either the specific inhibitor, AG825, in epidermal growth factor-treated C-33 LNCaP cells or ErbB-2 knockdown in C-81 LNCaP cells, reduced matriptase activation. These observations were confirmed by similar studies using both DU145 and PC3 cells. Together, these data suggest that ErbB-2 signaling plays an important role in matriptase zymogen activation. ErbB-2-enhanced matriptase activation was suppressed by a phosphatidylinositol 3-kinase inhibitor (ie, LY294002) but not by a MEK inhibitor (ie, PD98059). Suppression of matriptase expression by small hairpin RNA knockdown in ErbB-2-overexpressing LNCaP cells dramatically suppressed cancer cell invasion. In summary, our data indicate that ErbB-2 signaling via the phosphatidylinositol 3-kinase pathway results in up-regulated matriptase zymogen activity, which contributes to PCa cell invasion. Copyright ? American Society for Investigative Pathology. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-78650207591&doi=10.2353%2fajpath.2010.100228&partnerID=40&md5=176b766389ce7798bde9f1eaad3fb263 https://scholars.lib.ntu.edu.tw/handle/123456789/593877 |
ISSN: | 0002-9440 | DOI: | 10.2353/ajpath.2010.100228 | SDG/Keyword: | 2 (2 amino 3 methoxyphenyl)chromone; 2 morpholino 8 phenylchromone; 5 (2 benzothiazolyl)thiomethyl 4 hydroxy 3 methoxybenzylidenecyanoacetamide; epidermal growth factor receptor 2; matriptase; mitogen activated protein kinase 1; mitogen activated protein kinase 3; article; cancer cell; cancer growth; cancer invasion; cell migration; cell motility; enzyme activation; gene overexpression; human; human cell; phenotype; priority journal; prostate cancer; upregulation [SDGs]SDG3 |
Appears in Collections: | 免疫學研究所 |
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