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Conference Paper: Hepatocyte growth factor phosphorylates p70 S6 kinase to regulate Rac1 and Cdc42 and promote ovarian cancer cell migration and invasion

TitleHepatocyte growth factor phosphorylates p70 S6 kinase to regulate Rac1 and Cdc42 and promote ovarian cancer cell migration and invasion
Authors
Issue Date2009
PublisherAmerican Association for Cancer Research
Citation
The 100th AACR Annual Meeting, Denver, CO., 18-22 April 2009. In Cancer Research, 2009, v. 69 n. 9S, Abstract no. 3883 How to Cite?
AbstractOvarian cancer is the most lethal gynecological cancer. The hepatocyte growth factor (HGF) receptor Met is a receptor tyrosine kinase that is frequently overexpressed in ovarian cancer and correlates with poor prognosis. However, the molecular mechanisms responsible are still poorly understood. Our recent findings show for the first time that activation of p70 S6 kinase (p70S6K) downstream of phosphatidylinositol 3-kinase is a key step for HGF-induced invasion and migration of ovarian cancer cells. In this study, we showed that ectopic expression of active p70S6K induced dramatic reorganization of the actin cytoskeleton. This effect was associated with activation of two members of the Rho family of GTPases, Rac1 and Cdc42, but not RhoA. Inhibition of p70S6K by a specific inhibitor or small interfering RNA abolished the HGF-stimulated migratory phenotype with a concomitant reduction in Rac1 and Cdc42 activation, confirming the effect was p70S6K specific. Overexpression of constitutively active forms of Rac1 and Cdc42 were sufficient to induce cell migration, whereas dominant negative mutants of Rac1 and Cdc42 inhibited p70S6K-induced motogenic signal. Importantly, we showed that active p70S6K co-precipitated with F-actin in vitro. Immunofluorescence experiments confirmed that active p70S6K colocalized in vivo with the actin filaments. These results identify a novel mechanism in HGF-induced cellular invasion and migration, which is mediated by p70S6K through regulation of the actin cytoskeleton by Rho GTPases (This work is supported by Hong Kong Research Grants Council Grant HKU7599/05M to A.S.T.W.).
DescriptionConference Theme: Science, Synergy, and Success
Persistent Identifierhttp://hdl.handle.net/10722/187990
ISSN
2015 Impact Factor: 8.556
2015 SCImago Journal Rankings: 5.372

 

DC FieldValueLanguage
dc.contributor.authorIP, CKMen_US
dc.contributor.authorWong, ASTen_US
dc.date.accessioned2013-08-21T07:24:42Z-
dc.date.available2013-08-21T07:24:42Z-
dc.date.issued2009en_US
dc.identifier.citationThe 100th AACR Annual Meeting, Denver, CO., 18-22 April 2009. In Cancer Research, 2009, v. 69 n. 9S, Abstract no. 3883en_US
dc.identifier.issn0008-5472-
dc.identifier.urihttp://hdl.handle.net/10722/187990-
dc.descriptionConference Theme: Science, Synergy, and Success-
dc.description.abstractOvarian cancer is the most lethal gynecological cancer. The hepatocyte growth factor (HGF) receptor Met is a receptor tyrosine kinase that is frequently overexpressed in ovarian cancer and correlates with poor prognosis. However, the molecular mechanisms responsible are still poorly understood. Our recent findings show for the first time that activation of p70 S6 kinase (p70S6K) downstream of phosphatidylinositol 3-kinase is a key step for HGF-induced invasion and migration of ovarian cancer cells. In this study, we showed that ectopic expression of active p70S6K induced dramatic reorganization of the actin cytoskeleton. This effect was associated with activation of two members of the Rho family of GTPases, Rac1 and Cdc42, but not RhoA. Inhibition of p70S6K by a specific inhibitor or small interfering RNA abolished the HGF-stimulated migratory phenotype with a concomitant reduction in Rac1 and Cdc42 activation, confirming the effect was p70S6K specific. Overexpression of constitutively active forms of Rac1 and Cdc42 were sufficient to induce cell migration, whereas dominant negative mutants of Rac1 and Cdc42 inhibited p70S6K-induced motogenic signal. Importantly, we showed that active p70S6K co-precipitated with F-actin in vitro. Immunofluorescence experiments confirmed that active p70S6K colocalized in vivo with the actin filaments. These results identify a novel mechanism in HGF-induced cellular invasion and migration, which is mediated by p70S6K through regulation of the actin cytoskeleton by Rho GTPases (This work is supported by Hong Kong Research Grants Council Grant HKU7599/05M to A.S.T.W.).-
dc.languageengen_US
dc.publisherAmerican Association for Cancer Research-
dc.relation.ispartofCancer Researchen_US
dc.titleHepatocyte growth factor phosphorylates p70 S6 kinase to regulate Rac1 and Cdc42 and promote ovarian cancer cell migration and invasionen_US
dc.typeConference_Paperen_US
dc.identifier.emailWong, AST: awong1@hkucc.hku.hken_US
dc.identifier.authorityWong, AST=rp00805en_US
dc.description.naturelink_to_OA_fulltext-
dc.identifier.hkuros158504en_US
dc.identifier.hkuros218044-
dc.publisher.placeUnited States-

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