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Matriptase is involved in ErbB-2-induced prostate cancer cell invasion.
Am J Pathol 2010; 177(6):3145-58AJ

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.

Authors+Show Affiliations

Department of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, R817, 8F, No. 1, Section 1, Jen-Ai Rd, Taipei, Taiwan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20971737

Citation

Wu, Shang-Ru, et al. "Matriptase Is Involved in ErbB-2-induced Prostate Cancer Cell Invasion." The American Journal of Pathology, vol. 177, no. 6, 2010, pp. 3145-58.
Wu SR, Cheng TS, Chen WC, et al. Matriptase is involved in ErbB-2-induced prostate cancer cell invasion. Am J Pathol. 2010;177(6):3145-58.
Wu, S. R., Cheng, T. S., Chen, W. C., Shyu, H. Y., Ko, C. J., Huang, H. P., ... Lee, M. S. (2010). Matriptase is involved in ErbB-2-induced prostate cancer cell invasion. The American Journal of Pathology, 177(6), pp. 3145-58. doi:10.2353/ajpath.2010.100228.
Wu SR, et al. Matriptase Is Involved in ErbB-2-induced Prostate Cancer Cell Invasion. Am J Pathol. 2010;177(6):3145-58. PubMed PMID: 20971737.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Matriptase is involved in ErbB-2-induced prostate cancer cell invasion. AU - Wu,Shang-Ru, AU - Cheng,Tai-Shan, AU - Chen,Wen-Chi, AU - Shyu,Hsin-Yi, AU - Ko,Chun-Jung, AU - Huang,Hsiang-Po, AU - Teng,Chen-Hsin, AU - Lin,Chia-Hau, AU - Johnson,Michael D, AU - Lin,Chen-Yong, AU - Lee,Ming-Shyue, Y1 - 2010/10/22/ PY - 2010/10/26/entrez PY - 2010/10/26/pubmed PY - 2011/3/16/medline SP - 3145 EP - 58 JF - The American journal of pathology JO - Am. J. Pathol. VL - 177 IS - 6 N2 - 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. SN - 1525-2191 UR - https://www.unboundmedicine.com/medline/citation/20971737/Matriptase_is_involved_in_ErbB_2_induced_prostate_cancer_cell_invasion_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0002-9440(10)62938-0 DB - PRIME DP - Unbound Medicine ER -