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Article: Overexpressed PAK4 promotes proliferation, migration and invasion of choriocarcinoma
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TitleOverexpressed PAK4 promotes proliferation, migration and invasion of choriocarcinoma
 
AuthorsZhang, HJ2 3
Siu, MKY2
Yeung, MCW2
Jiang, LL2
Mak, VCY2
Ngan, HYS2
Wong, OGW2
Zhang, HQ1 4
Cheung, ANY2
 
Issue Date2011
 
PublisherOxford University Press. The Journal's web site is located at http://carcin.oxfordjournals.org/
 
CitationCarcinogenesis, 2011, v. 32 n. 5, p. 765-771 [How to Cite?]
DOI: http://dx.doi.org/10.1093/carcin/bgr033
 
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.
 
ISSN0143-3334
2013 Impact Factor: 5.266
 
DOIhttp://dx.doi.org/10.1093/carcin/bgr033
 
ISI Accession Number IDWOS:000290341000015
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).

 
ReferencesReferences in Scopus
 
GrantsAkt and p21-activated kinase signaling pathways in gestational trophoblastic disease
 
DC FieldValue
dc.contributor.authorZhang, HJ
 
dc.contributor.authorSiu, MKY
 
dc.contributor.authorYeung, MCW
 
dc.contributor.authorJiang, LL
 
dc.contributor.authorMak, VCY
 
dc.contributor.authorNgan, HYS
 
dc.contributor.authorWong, OGW
 
dc.contributor.authorZhang, HQ
 
dc.contributor.authorCheung, ANY
 
dc.date.accessioned2011-09-23T06:01:58Z
 
dc.date.available2011-09-23T06:01:58Z
 
dc.date.issued2011
 
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.
 
dc.description.naturelink_to_subscribed_fulltext
 
dc.identifier.citationCarcinogenesis, 2011, v. 32 n. 5, p. 765-771 [How to Cite?]
DOI: http://dx.doi.org/10.1093/carcin/bgr033
 
dc.identifier.citeulike9286692
 
dc.identifier.doihttp://dx.doi.org/10.1093/carcin/bgr033
 
dc.identifier.eissn1460-2180
 
dc.identifier.epage771
 
dc.identifier.hkuros192477
 
dc.identifier.isiWOS:000290341000015
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).

 
dc.identifier.issn0143-3334
2013 Impact Factor: 5.266
 
dc.identifier.issue5
 
dc.identifier.openurl
 
dc.identifier.pmid21325635
 
dc.identifier.scopuseid_2-s2.0-79955766598
 
dc.identifier.spage765
 
dc.identifier.urihttp://hdl.handle.net/10722/139934
 
dc.identifier.volume32
 
dc.languageeng
 
dc.publisherOxford University Press. The Journal's web site is located at http://carcin.oxfordjournals.org/
 
dc.publisher.placeUnited Kingdom
 
dc.relation.ispartofCarcinogenesis
 
dc.relation.projectAkt and p21-activated kinase signaling pathways in gestational trophoblastic disease
 
dc.relation.referencesReferences in Scopus
 
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 choriocarcinoma
 
dc.typeArticle
 
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Author Affiliations
  1. School of Basic Medical Sciences
  2. The University of Hong Kong
  3. Shanghai Jiaotong University
  4. Peking University