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Article: Activation of p70S6K induces expression of matrix metalloproteinase 9 associated with hepatocyte growth factor-mediated invasion in human ovarian cancer cells

TitleActivation of p70S6K induces expression of matrix metalloproteinase 9 associated with hepatocyte growth factor-mediated invasion in human ovarian cancer cells
Authors
Issue Date2006
PublisherThe Endocrine Society. The Journal's web site is located at http://endo.endojournals.org
Citation
Endocrinology, 2006, v. 147 n. 5, p. 2557-2566 How to Cite?
AbstractThe expression of hepatocyte growth factor (HGF) receptor, encoded by the Met oncogene, is elevated in ovarian and a variety of cancers. Here we show that human ovarian cancer cells with high Met expression were more sensitive to the cell motility and invasion effect of HGF. Met down-regulation by small interfering RNAs or K252a resulted in reduced migration in response to HGF. The invasive/migratory phenotype activated by HGF can be blocked by specific inhibitors of the phosphatidylinositol-3-kinase (PI3K) cascade, inhibitor of p70 S6K, and also the expression of a dominant-negative Akt, demonstrating that HGF transmits the motogenic signal through PI3K and Akt to p70 S6K. A significant role for p70 S6K in cell invasion is further supported by the observation that expression of constitutively active forms of p70 S6K is sufficient to induce invasive and migratory phenotypes in ovarian cancer cells. Importantly, activation of p70 S6K stimulated expression and proteolytic activity of matrix metalloproteinase (MMP)-9 and cellular invasion, whereas it had little effect on MMP-2, suggesting for the first time that MMP-9 up-regulation by p70 S6K as a key step for HGF-induced invasion and migration. These data suggest that interfering p70 S6K may provide a novel means of controlling tumor cell invasiveness. Copyright © 2006 by The Endocrine Society.
Persistent Identifierhttp://hdl.handle.net/10722/84598
ISSN
2015 Impact Factor: 4.159
2015 SCImago Journal Rankings: 2.363
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorZhou, HYen_HK
dc.contributor.authorWong, ASTen_HK
dc.date.accessioned2010-09-06T08:54:54Z-
dc.date.available2010-09-06T08:54:54Z-
dc.date.issued2006en_HK
dc.identifier.citationEndocrinology, 2006, v. 147 n. 5, p. 2557-2566en_HK
dc.identifier.issn0013-7227en_HK
dc.identifier.urihttp://hdl.handle.net/10722/84598-
dc.description.abstractThe expression of hepatocyte growth factor (HGF) receptor, encoded by the Met oncogene, is elevated in ovarian and a variety of cancers. Here we show that human ovarian cancer cells with high Met expression were more sensitive to the cell motility and invasion effect of HGF. Met down-regulation by small interfering RNAs or K252a resulted in reduced migration in response to HGF. The invasive/migratory phenotype activated by HGF can be blocked by specific inhibitors of the phosphatidylinositol-3-kinase (PI3K) cascade, inhibitor of p70 S6K, and also the expression of a dominant-negative Akt, demonstrating that HGF transmits the motogenic signal through PI3K and Akt to p70 S6K. A significant role for p70 S6K in cell invasion is further supported by the observation that expression of constitutively active forms of p70 S6K is sufficient to induce invasive and migratory phenotypes in ovarian cancer cells. Importantly, activation of p70 S6K stimulated expression and proteolytic activity of matrix metalloproteinase (MMP)-9 and cellular invasion, whereas it had little effect on MMP-2, suggesting for the first time that MMP-9 up-regulation by p70 S6K as a key step for HGF-induced invasion and migration. These data suggest that interfering p70 S6K may provide a novel means of controlling tumor cell invasiveness. Copyright © 2006 by The Endocrine Society.en_HK
dc.languageengen_HK
dc.publisherThe Endocrine Society. The Journal's web site is located at http://endo.endojournals.orgen_HK
dc.relation.ispartofEndocrinologyen_HK
dc.rightsEndocrinology. Copyright © The Endocrine Society.en_HK
dc.titleActivation of p70S6K induces expression of matrix metalloproteinase 9 associated with hepatocyte growth factor-mediated invasion in human ovarian cancer cellsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0013-7227&volume=147&spage=2557&epage=2566&date=2006&atitle=Activation+of+p70S6K+induces+expression+of+matrix+metalloproteinase+9+associated+with+hepatocyte+growth+factor-mediated+invasion+in+human+ovarian+cancer+cellsen_HK
dc.identifier.emailWong, AST: awong1@hkucc.hku.hken_HK
dc.identifier.authorityWong, AST=rp00805en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1210/en.2005-1404en_HK
dc.identifier.pmid16469801-
dc.identifier.scopuseid_2-s2.0-33645856178en_HK
dc.identifier.hkuros120952en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-33645856178&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume147en_HK
dc.identifier.issue5en_HK
dc.identifier.spage2557en_HK
dc.identifier.epage2566en_HK
dc.identifier.isiWOS:000236830600058-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridZhou, HY=7404742310en_HK
dc.identifier.scopusauthoridWong, AST=23987963300en_HK

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