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Article: Overexpressed PAK4 promotes proliferation, migration and invasion of choriocarcinoma

TitleOverexpressed PAK4 promotes proliferation, migration and invasion of choriocarcinoma
Authors
Issue Date2011
PublisherOxford University Press. The Journal's web site is located at http://carcin.oxfordjournals.org/
Citation
Carcinogenesis, 2011, v. 32 n. 5, p. 765-771 How to Cite?
Abstract
Gestational trophoblastic disease (GTD) includes frankly malignant choriocarcinoma (CCA) and placental site trophoblastic tumor and potentially malignant hydatidiform mole. p21-Activated kinase (PAK) 4 promotes cell motility. This study investigated the role of PAK4 in the pathogenesis of GTD. PAK4 messenger RNA and protein expressions in clinical samples and cell lines of normal placentas and GTD were determined by quantitative realtime polymerase chain reaction and western blot, respectively. The effects of human chorionic gonadotropin (hCG) and phosphoinositide 3 kinase (PI3K) on the expression and activation of PAK4 were investigated by treating CCA JEG3 and JAR cells with anti-hCG antibody and PI3K inhibitor, respectively. The effects of PAK4 on CCA cell proliferation, migration and invasion were assessed by corresponding functional assays. We demonstrated overexpression of PAK4 in GTD and CCA cell lines at both RNA and protein level. hCGis one of the upstreamregulators of PAK4 expression, whereas activation of PAK4 is PI3K/PKB dependent in JEG3 and JAR cells. Significant correlation was found between PAK4 expression and proliferation index minichromosome maintenance complex component 7 (P5 0.007). In JEG3 and JAR cells, stably transfected PAK4 increased proliferation, migration and invasion, whereas small interfering RNA knockdown of PAK4 decreased proliferation, migration and invasion along with downregulated CDK6 and membrane-type 1 matrix metalloproteinase (MT1-MMP) and upregulated p16. We further found PAK4-mediated transcription of MT1-MMP in CCA cells by luciferase reporter assay. Our results demonstrated for the first time that overexpressed PAK4 was involved in the pathogenesis of GTD, promoting proliferation and enhancing cell migration and invasion in CCA cells. © The Author 2011. Published by Oxford University Press. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/139934
ISSN
2013 Impact Factor: 5.266
ISI Accession Number ID
Funding AgencyGrant Number
Research Grants Council of the Hong Kong Special Administrative RegionHKU 7503/06M
Funding Information:

Research Grants Council of the Hong Kong Special Administrative Region (HKU 7503/06M).

References
Grants

 

DC FieldValueLanguage
dc.contributor.authorZhang, HJen_HK
dc.contributor.authorSiu, MKYen_HK
dc.contributor.authorYeung, MCWen_HK
dc.contributor.authorJiang, LLen_HK
dc.contributor.authorMak, VCYen_HK
dc.contributor.authorNgan, HYSen_HK
dc.contributor.authorWong, OGWen_HK
dc.contributor.authorZhang, HQen_HK
dc.contributor.authorCheung, ANYen_HK
dc.date.accessioned2011-09-23T06:01:58Z-
dc.date.available2011-09-23T06:01:58Z-
dc.date.issued2011en_HK
dc.identifier.citationCarcinogenesis, 2011, v. 32 n. 5, p. 765-771en_HK
dc.identifier.issn0143-3334en_HK
dc.identifier.urihttp://hdl.handle.net/10722/139934-
dc.description.abstractGestational trophoblastic disease (GTD) includes frankly malignant choriocarcinoma (CCA) and placental site trophoblastic tumor and potentially malignant hydatidiform mole. p21-Activated kinase (PAK) 4 promotes cell motility. This study investigated the role of PAK4 in the pathogenesis of GTD. PAK4 messenger RNA and protein expressions in clinical samples and cell lines of normal placentas and GTD were determined by quantitative realtime polymerase chain reaction and western blot, respectively. The effects of human chorionic gonadotropin (hCG) and phosphoinositide 3 kinase (PI3K) on the expression and activation of PAK4 were investigated by treating CCA JEG3 and JAR cells with anti-hCG antibody and PI3K inhibitor, respectively. The effects of PAK4 on CCA cell proliferation, migration and invasion were assessed by corresponding functional assays. We demonstrated overexpression of PAK4 in GTD and CCA cell lines at both RNA and protein level. hCGis one of the upstreamregulators of PAK4 expression, whereas activation of PAK4 is PI3K/PKB dependent in JEG3 and JAR cells. Significant correlation was found between PAK4 expression and proliferation index minichromosome maintenance complex component 7 (P5 0.007). In JEG3 and JAR cells, stably transfected PAK4 increased proliferation, migration and invasion, whereas small interfering RNA knockdown of PAK4 decreased proliferation, migration and invasion along with downregulated CDK6 and membrane-type 1 matrix metalloproteinase (MT1-MMP) and upregulated p16. We further found PAK4-mediated transcription of MT1-MMP in CCA cells by luciferase reporter assay. Our results demonstrated for the first time that overexpressed PAK4 was involved in the pathogenesis of GTD, promoting proliferation and enhancing cell migration and invasion in CCA cells. © The Author 2011. Published by Oxford University Press. All rights reserved.en_HK
dc.languageengen_US
dc.publisherOxford University Press. The Journal's web site is located at http://carcin.oxfordjournals.org/en_HK
dc.relation.ispartofCarcinogenesisen_HK
dc.subject.meshCell Movement-
dc.subject.meshCell Proliferation-
dc.subject.meshChoriocarcinoma - genetics - metabolism - pathology-
dc.subject.meshUterine Neoplasms - genetics - metabolism - pathology-
dc.subject.meshp21-Activated Kinases - antagonists and inhibitors - genetics - metabolism-
dc.titleOverexpressed PAK4 promotes proliferation, migration and invasion of choriocarcinomaen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0143-3334&volume=32&issue=5&spage=765&epage=771&date=2011&atitle=Overexpressed+PAK4+promotes+proliferation,+migration+and+invasion+of+choriocarcinoma-
dc.identifier.emailSiu, MKY: mkysiu@hkucc.hku.hken_HK
dc.identifier.emailNgan, HYS: hysngan@hkucc.hku.hken_HK
dc.identifier.emailCheung, ANY: anycheun@hkucc.hku.hken_HK
dc.identifier.authoritySiu, MKY=rp00275en_HK
dc.identifier.authorityNgan, HYS=rp00346en_HK
dc.identifier.authorityCheung, ANY=rp00542en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1093/carcin/bgr033en_HK
dc.identifier.pmid21325635en_HK
dc.identifier.scopuseid_2-s2.0-79955766598en_HK
dc.identifier.hkuros192477en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-79955766598&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume32en_HK
dc.identifier.issue5en_HK
dc.identifier.spage765en_HK
dc.identifier.epage771en_HK
dc.identifier.eissn1460-2180-
dc.identifier.isiWOS:000290341000015-
dc.publisher.placeUnited Kingdomen_HK
dc.relation.projectAkt and p21-activated kinase signaling pathways in gestational trophoblastic disease-
dc.identifier.scopusauthoridZhang, HJ=26666421300en_HK
dc.identifier.scopusauthoridSiu, MKY=24924018400en_HK
dc.identifier.scopusauthoridYeung, MCW=7101861644en_HK
dc.identifier.scopusauthoridJiang, LL=36801738800en_HK
dc.identifier.scopusauthoridMak, VCY=36508943200en_HK
dc.identifier.scopusauthoridNgan, HYS=34571944100en_HK
dc.identifier.scopusauthoridWong, OGW=7004813981en_HK
dc.identifier.scopusauthoridZhang, HQ=43761720200en_HK
dc.identifier.scopusauthoridCheung, ANY=54927484100en_HK
dc.identifier.citeulike9286692-

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