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Article: Differential expression and phosphorylation of Pak1 and Pak2 in ovarian cancer: Effects on prognosis and cell invasion
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TitleDifferential expression and phosphorylation of Pak1 and Pak2 in ovarian cancer: Effects on prognosis and cell invasion
 
AuthorsSiu, MKY1
Wong, ESY1
Chan, HY1
Kong, DSH1
Woo, NWS1
Tam, KF1
Ngan, HYS1
Chan, QKY1
Chan, DCW1
Chan, KYK1
Cheung, ANY1
 
KeywordsCell invasion
Ovarian cancer
Pak1
Pak2
Phosphorylation
Prognosis
 
Issue Date2010
 
PublisherJohn Wiley & Sons, Inc.. The Journal's web site is located at http://www3.interscience.wiley.com/journal/29331/home
 
CitationInternational Journal Of Cancer, 2010, v. 127 n. 1, p. 21-31 [How to Cite?]
DOI: http://dx.doi.org/10.1002/ijc.25005
 
AbstractOvarian cancer is a gynecological malignancy with high mortality. Therefore, the identification of novel prognostic and therapeutic targets is important. p21-activated kinases (Paks) are involved in cytoskeleton reorganization. This study investigated the clinical significance of total and phosphorylated (p) Pak1 and Pak2 as well as their functional roles in ovarian cancer. Expressions of Pak1, p-Pak1 Thr 212, Pak2 and p-Pak2 Ser 20 in ovarian normal and cancerous cell lines as well as in clinical samples of ovarian tumors were evaluated. The effects of Pak1 and Pak2 on ovarian cancer cell functions were determined. Pak1, p-Pak1 and p-Pak2 were overexpressed in ovarian cancer cell lines, and clinical samples of ovarian cancers were compared with benign ovarian lesions/inclusion cysts. Similar Pak2 expression levels were observed among normal and cancerous cell lines and clinical samples. After multiple testing correction, high Pak1 and nuclear p-Pak1 expression in ovarian cancers was significantly associated with histological type and tumor grade, respectively. Pak1 and p-Pak1 expression was associated with poor overall and disease-free survival. Pak1 was an independent prognostic factor. Knockdown of Pak1 and Pak2 in ovarian cancer cell lines reduced cell migration and invasion but did not affect cell proliferation and apoptosis. Knockdown of Pak1 also reduced p38 activation and downregulated vascular endothelial growth factor. Conversely, ectopic Pak1 overexpression enhanced ovarian cancer cell migration and invasion in a kinase-dependent manner, along with increased p38 activation. Our findings suggest that Pak1, p-Pak1 and p-Pak2 play important roles in ovarian carcinogenesis. Pak1 and p-Pak1 may be potential prognostic markers and therapeutic molecular targets in ovarian cancer. © 2010 UICC.
 
ISSN0020-7136
2013 Impact Factor: 5.007
 
DOIhttp://dx.doi.org/10.1002/ijc.25005
 
ISI Accession Number IDWOS:000278148800003
Funding AgencyGrant Number
Council of the Hong Kong Special Administrative RegionHKU 7503/06M
Hong Kong Anti-Cancer Society, University of Hong Kong
Funding Information:

Grant sponsor: Research Grants Council of the Hong Kong Special Administrative Region; Grant number: HKU 7503/06M; Grant Sponsors: Hong Kong Anti-Cancer Society, University of Hong Kong

 
ReferencesReferences in Scopus
 
GrantsAkt and p21-activated kinase signaling pathways in gestational trophoblastic disease
 
DC FieldValue
dc.contributor.authorSiu, MKY
 
dc.contributor.authorWong, ESY
 
dc.contributor.authorChan, HY
 
dc.contributor.authorKong, DSH
 
dc.contributor.authorWoo, NWS
 
dc.contributor.authorTam, KF
 
dc.contributor.authorNgan, HYS
 
dc.contributor.authorChan, QKY
 
dc.contributor.authorChan, DCW
 
dc.contributor.authorChan, KYK
 
dc.contributor.authorCheung, ANY
 
dc.date.accessioned2010-10-31T12:44:25Z
 
dc.date.available2010-10-31T12:44:25Z
 
dc.date.issued2010
 
dc.description.abstractOvarian cancer is a gynecological malignancy with high mortality. Therefore, the identification of novel prognostic and therapeutic targets is important. p21-activated kinases (Paks) are involved in cytoskeleton reorganization. This study investigated the clinical significance of total and phosphorylated (p) Pak1 and Pak2 as well as their functional roles in ovarian cancer. Expressions of Pak1, p-Pak1 Thr 212, Pak2 and p-Pak2 Ser 20 in ovarian normal and cancerous cell lines as well as in clinical samples of ovarian tumors were evaluated. The effects of Pak1 and Pak2 on ovarian cancer cell functions were determined. Pak1, p-Pak1 and p-Pak2 were overexpressed in ovarian cancer cell lines, and clinical samples of ovarian cancers were compared with benign ovarian lesions/inclusion cysts. Similar Pak2 expression levels were observed among normal and cancerous cell lines and clinical samples. After multiple testing correction, high Pak1 and nuclear p-Pak1 expression in ovarian cancers was significantly associated with histological type and tumor grade, respectively. Pak1 and p-Pak1 expression was associated with poor overall and disease-free survival. Pak1 was an independent prognostic factor. Knockdown of Pak1 and Pak2 in ovarian cancer cell lines reduced cell migration and invasion but did not affect cell proliferation and apoptosis. Knockdown of Pak1 also reduced p38 activation and downregulated vascular endothelial growth factor. Conversely, ectopic Pak1 overexpression enhanced ovarian cancer cell migration and invasion in a kinase-dependent manner, along with increased p38 activation. Our findings suggest that Pak1, p-Pak1 and p-Pak2 play important roles in ovarian carcinogenesis. Pak1 and p-Pak1 may be potential prognostic markers and therapeutic molecular targets in ovarian cancer. © 2010 UICC.
 
dc.description.natureLink_to_subscribed_fulltext
 
dc.identifier.citationInternational Journal Of Cancer, 2010, v. 127 n. 1, p. 21-31 [How to Cite?]
DOI: http://dx.doi.org/10.1002/ijc.25005
 
dc.identifier.doihttp://dx.doi.org/10.1002/ijc.25005
 
dc.identifier.epage31
 
dc.identifier.hkuros174761
 
dc.identifier.isiWOS:000278148800003
Funding AgencyGrant Number
Council of the Hong Kong Special Administrative RegionHKU 7503/06M
Hong Kong Anti-Cancer Society, University of Hong Kong
Funding Information:

Grant sponsor: Research Grants Council of the Hong Kong Special Administrative Region; Grant number: HKU 7503/06M; Grant Sponsors: Hong Kong Anti-Cancer Society, University of Hong Kong

 
dc.identifier.issn0020-7136
2013 Impact Factor: 5.007
 
dc.identifier.issue1
 
dc.identifier.openurl
 
dc.identifier.pmid19876919
 
dc.identifier.scopuseid_2-s2.0-77953465926
 
dc.identifier.spage21
 
dc.identifier.urihttp://hdl.handle.net/10722/126717
 
dc.identifier.volume127
 
dc.languageeng
 
dc.publisherJohn Wiley & Sons, Inc.. The Journal's web site is located at http://www3.interscience.wiley.com/journal/29331/home
 
dc.publisher.placeUnited States
 
dc.relation.ispartofInternational Journal of Cancer
 
dc.relation.projectAkt and p21-activated kinase signaling pathways in gestational trophoblastic disease
 
dc.relation.referencesReferences in Scopus
 
dc.subject.meshApoptosis
 
dc.subject.meshBase Sequence
 
dc.subject.meshBlotting, Western
 
dc.subjectCell invasion
 
dc.subjectOvarian cancer
 
dc.subjectPak1
 
dc.subjectPak2
 
dc.subjectPhosphorylation
 
dc.subjectPrognosis
 
dc.titleDifferential expression and phosphorylation of Pak1 and Pak2 in ovarian cancer: Effects on prognosis and cell invasion
 
dc.typeArticle
 
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Author Affiliations
  1. The University of Hong Kong