The Rho/ROCK pathway for lysophosphatidic acid-induced proteolytic enzyme expression and ovarian cancer cell invasion
DC Field | Value | Language |
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dc.contributor.author | Jeong, K. J. | - |
dc.contributor.author | Park, S. Y. | - |
dc.contributor.author | Cho, K. H. | - |
dc.contributor.author | Sohn, J. S. | - |
dc.contributor.author | Lee, J. | - |
dc.contributor.author | Kim, Y. K. | - |
dc.contributor.author | Kang, J. | - |
dc.contributor.author | Park, C. G. | - |
dc.contributor.author | Han, J. W. | - |
dc.contributor.author | Lee, H. Y. | - |
dc.date.available | 2021-02-22T12:45:48Z | - |
dc.date.issued | 2012-09 | - |
dc.identifier.issn | 0950-9232 | - |
dc.identifier.issn | 1476-5594 | - |
dc.identifier.uri | https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/11846 | - |
dc.description.abstract | Lysophosphatidic acid (LPA) is a biolipid that has diverse biological activities implicated in ovarian cancer initiation and progression. Previous studies have shown the critical role of the Rho/Rho-associated kinase (ROCK) pathway in LPA-induced ovarian cancer progression. However, detailed underlying mechanism by which the Rho/ROCK pathway induces ovarian cancer cell invasion is still incompletely understood. In the present study, we observed that the Rho/ROCK pathway is implicated in the production of proteolytic enzymes, leading to LPA-induced ovarian cancer cell invasion. LPA induced matrix metalloproteinase (MMP)-9 expression in CAOV-3 and PA-1 cells and urokinase-type plasminogen activator (uPA) expression in SKOV-3 cells. LPA-induced proteolytic enzyme expression was required for the invasion of ovarian cancer cells expressing corresponding enzymes. Pretreatment of cells with a pharmacological inhibitor of Rho/ROCK (Y-27632) or overexpression of a dominant-negative mutant of Rho (Rho N19) profoundly inhibited LPA-induced proteolytic enzyme expression as well as the invasive potential of ovarian cancer cells. In addition, transfection with dominant-negative Ras (Ras N17) significantly inhibited LPA-induced Rho activation as well as MMP-9 and uPA expression. Consistently, Y-27632 reduced LPA-induced nuclear factor (NF)-kappa B activation that is critical for proteolytic enzyme expression and cellular invasion. Collectively, we demonstrate a mechanism by which LPA promotes ovarian cancer progression through coordinate activation of a Ras/Rho/ROCK/NF-kappa B signaling pathway and the proteolytic enzyme secretion, providing novel biomarkers and promising therapeutic targets for ovarian cancer cell progression. Oncogene (2012) 31, 4279-4289; doi:10.1038/onc.2011.595; published online 16 January 2012 | - |
dc.format.extent | 11 | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | NATURE PUBLISHING GROUP | - |
dc.title | The Rho/ROCK pathway for lysophosphatidic acid-induced proteolytic enzyme expression and ovarian cancer cell invasion | - |
dc.type | Article | - |
dc.publisher.location | 영국 | - |
dc.identifier.doi | 10.1038/onc.2011.595 | - |
dc.identifier.scopusid | 2-s2.0-84867083414 | - |
dc.identifier.wosid | 000309520200003 | - |
dc.identifier.bibliographicCitation | ONCOGENE, v.31, no.39, pp 4279 - 4289 | - |
dc.citation.title | ONCOGENE | - |
dc.citation.volume | 31 | - |
dc.citation.number | 39 | - |
dc.citation.startPage | 4279 | - |
dc.citation.endPage | 4289 | - |
dc.type.docType | Article | - |
dc.description.isOpenAccess | N | - |
dc.description.journalRegisteredClass | sci | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
dc.relation.journalResearchArea | Oncology | - |
dc.relation.journalResearchArea | Cell Biology | - |
dc.relation.journalResearchArea | Genetics & Heredity | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Oncology | - |
dc.relation.journalWebOfScienceCategory | Cell Biology | - |
dc.relation.journalWebOfScienceCategory | Genetics & Heredity | - |
dc.subject.keywordPlus | NF-KAPPA-B | - |
dc.subject.keywordPlus | MATRIX-DEGRADING PROTEINASES | - |
dc.subject.keywordPlus | HUMAN UROKINASE GENE | - |
dc.subject.keywordPlus | RHO-GTPASES | - |
dc.subject.keywordPlus | CARCINOMA CELLS | - |
dc.subject.keywordPlus | MATRIX-METALLOPROTEINASE-9 EXPRESSION | - |
dc.subject.keywordPlus | PLASMINOGEN-ACTIVATOR | - |
dc.subject.keywordPlus | MEMBRANE-VESICLES | - |
dc.subject.keywordPlus | FOCAL ADHESION | - |
dc.subject.keywordPlus | GROWTH-FACTORS | - |
dc.subject.keywordAuthor | LPA | - |
dc.subject.keywordAuthor | Rho/ROCK | - |
dc.subject.keywordAuthor | invasion | - |
dc.subject.keywordAuthor | uPA | - |
dc.subject.keywordAuthor | MMP-9 | - |
dc.subject.keywordAuthor | ovarian cancer | - |
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