Source:http://linkedlifedata.com/resource/pubmed/id/17187779
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
2007-2-6
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pubmed:abstractText |
The present study investigated the role of integrin-linked kinase (ILK) in TGFbeta1-stimulated invasion/migration of human ovarian cancer cells. We investigated TGFbeta1 regulation of ILK, and effects of ILK knockdown on TGFbeta1-stimulated invasion/migration and the associated proteinase systems, urokinase plasminogen activator (uPA) and matrix metalloproteinases (MMPs) in SKOV3 cells. TGFbeta1 stimulated ILK kinase activity, and had no effect on ILK protein/mRNA levels. Transient transfection of an ILK-specific siRNA (ILK-H) reduced ILK protein level, mRNA level and kinase activity. ILK knockdown by ILK-H suppressed the basal and TGFbeta1-stimulated invasion and migration. Further, ILK-H reduced the basal and TGFbeta1-stimulated secretion of uPA, and increased the secretion of its inhibitor (PAI-1). Conversely, ILK-H did not affect TGFbeta1-stimulated secretion of MMP2 and its cell-associated activator MT1-MMP. Additionally, TGFbeta1 activated Smad2 phosphorylation, and this was not affected by ILK knockdown. Earlier reports indicate that Smad2 activation increased the expression of MMP2 and MT1-MMP. Thus, TGFbeta1 may act through ILK-independent and Smad2-dependent signaling in regulating MMP2 and MT1-MMP in SKOV3 cells. Collectively, this study suggests that ILK serves as a key mediator in TGFbeta1 regulation of uPA/PAI-1 system critical for the invasiveness of human ovarian cancer cells. And ILK is a potential target for cancer therapy.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Matrix Metalloproteinase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Plasminogen Activator Inhibitor 1,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/SERPINE1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta1,
http://linkedlifedata.com/resource/pubmed/chemical/Urokinase-Type Plasminogen Activator,
http://linkedlifedata.com/resource/pubmed/chemical/integrin-linked kinase
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0014-4827
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
313
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
602-13
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:17187779-Cell Line, Tumor,
pubmed-meshheading:17187779-Cell Movement,
pubmed-meshheading:17187779-Female,
pubmed-meshheading:17187779-Humans,
pubmed-meshheading:17187779-Matrix Metalloproteinase 2,
pubmed-meshheading:17187779-Neoplasm Invasiveness,
pubmed-meshheading:17187779-Ovarian Neoplasms,
pubmed-meshheading:17187779-Plasminogen Activator Inhibitor 1,
pubmed-meshheading:17187779-Protein-Serine-Threonine Kinases,
pubmed-meshheading:17187779-Transfection,
pubmed-meshheading:17187779-Transforming Growth Factor beta1,
pubmed-meshheading:17187779-Urokinase-Type Plasminogen Activator
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pubmed:year |
2007
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pubmed:articleTitle |
Critical involvement of ILK in TGFbeta1-stimulated invasion/migration of human ovarian cancer cells is associated with urokinase plasminogen activator system.
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pubmed:affiliation |
Institute of Physiology, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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