Document Detail


Matriptase is involved in ErbB-2-induced prostate cancer cell invasion.
MedLine Citation:
PMID:  20971737     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Shang-Ru Wu; Tai-Shan Cheng; Wen-Chi Chen; Hsin-Yi Shyu; Chun-Jung Ko; Hsiang-Po Huang; Chen-Hsin Teng; Chia-Hau Lin; Michael D Johnson; Chen-Yong Lin; Ming-Shyue Lee
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-10-22
Journal Detail:
Title:  The American journal of pathology     Volume:  177     ISSN:  1525-2191     ISO Abbreviation:  Am. J. Pathol.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-12-01     Completed Date:  2011-03-15     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  0370502     Medline TA:  Am J Pathol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3145-58     Citation Subset:  AIM; IM    
Affiliation:
Department of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, R817, 8F, No. 1, Section 1, Jen-Ai Rd, Taipei, Taiwan.
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MeSH Terms
Descriptor/Qualifier:
Androgens / pharmacology
Carcinoma / genetics,  pathology*
Cell Movement / drug effects,  genetics
Cells, Cultured
Disease Progression
Drug Resistance / drug effects,  genetics
Enzyme Activation / genetics
Gene Knockdown Techniques
Genes, erbB-2 / physiology*
Humans
Male
Neoplasm Invasiveness
Phosphatidylinositol 3-Kinases / metabolism,  physiology
Prostatic Neoplasms / genetics,  pathology*
RNA, Small Interfering / pharmacology
Receptor, erbB-2 / antagonists & inhibitors,  genetics,  metabolism
Serine Endopeptidases / genetics,  metabolism,  physiology*
Chemical
Reg. No./Substance:
0/Androgens; 0/RNA, Small Interfering; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC 2.7.10.1/ERBB2 protein, human; EC 2.7.10.1/Receptor, erbB-2; EC 3.4.21.-/Serine Endopeptidases; EC 3.4.21.109/ST14 protein, human
Comments/Corrections

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