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Article: Differential expression and phosphorylation of Pak1 and Pak2 in ovarian cancer: Effects on prognosis and cell invasion

TitleDifferential expression and phosphorylation of Pak1 and Pak2 in ovarian cancer: Effects on prognosis and cell invasion
Authors
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
Citation
International Journal Of Cancer, 2010, v. 127 n. 1, p. 21-31 How to Cite?
Abstract
Ovarian 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.
Persistent Identifierhttp://hdl.handle.net/10722/126717
ISSN
2013 Impact Factor: 5.007
ISI Accession Number ID
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

References
Grants

 

Author Affiliations
  1. The University of Hong Kong
DC FieldValueLanguage
dc.contributor.authorSiu, MKYen_HK
dc.contributor.authorWong, ESYen_HK
dc.contributor.authorChan, HYen_HK
dc.contributor.authorKong, DSHen_HK
dc.contributor.authorWoo, NWSen_HK
dc.contributor.authorTam, KFen_HK
dc.contributor.authorNgan, HYSen_HK
dc.contributor.authorChan, QKYen_HK
dc.contributor.authorChan, DCWen_HK
dc.contributor.authorChan, KYKen_HK
dc.contributor.authorCheung, ANYen_HK
dc.date.accessioned2010-10-31T12:44:25Z-
dc.date.available2010-10-31T12:44:25Z-
dc.date.issued2010en_HK
dc.identifier.citationInternational Journal Of Cancer, 2010, v. 127 n. 1, p. 21-31en_HK
dc.identifier.issn0020-7136en_HK
dc.identifier.urihttp://hdl.handle.net/10722/126717-
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.en_HK
dc.languageengen_HK
dc.publisherJohn Wiley & Sons, Inc.. The Journal's web site is located at http://www3.interscience.wiley.com/journal/29331/homeen_HK
dc.relation.ispartofInternational Journal of Canceren_HK
dc.subjectCell invasionen_HK
dc.subjectOvarian canceren_HK
dc.subjectPak1en_HK
dc.subjectPak2en_HK
dc.subjectPhosphorylationen_HK
dc.subjectPrognosisen_HK
dc.subject.meshApoptosis-
dc.subject.meshBase Sequence-
dc.subject.meshBlotting, Western-
dc.titleDifferential expression and phosphorylation of Pak1 and Pak2 in ovarian cancer: Effects on prognosis and cell invasionen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0020-7136&volume=127&issue=1&spage=21&epage=31&date=2010&atitle=Differential+expression+and+phosphorylation+of+Pak1+and+Pak2+in+ovarian+cancer:+effects+on+prognosis+and+cell+invasionen_HK
dc.identifier.emailSiu, MKY: mkysiu@hkucc.hku.hken_HK
dc.identifier.emailNgan, HYS: hysngan@hkucc.hku.hken_HK
dc.identifier.emailChan, KYK: kelvinc@pathology.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.authorityChan, KYK=rp00453en_HK
dc.identifier.authorityCheung, ANY=rp00542en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1002/ijc.25005en_HK
dc.identifier.pmid19876919en_HK
dc.identifier.scopuseid_2-s2.0-77953465926en_HK
dc.identifier.hkuros174761en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77953465926&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume127en_HK
dc.identifier.issue1en_HK
dc.identifier.spage21en_HK
dc.identifier.epage31en_HK
dc.identifier.isiWOS:000278148800003-
dc.publisher.placeUnited Statesen_HK
dc.relation.projectAkt and p21-activated kinase signaling pathways in gestational trophoblastic disease-
dc.identifier.scopusauthoridSiu, MKY=24924018400en_HK
dc.identifier.scopusauthoridWong, ESY=23101622300en_HK
dc.identifier.scopusauthoridChan, HY=26024081600en_HK
dc.identifier.scopusauthoridKong, DSH=36113859000en_HK
dc.identifier.scopusauthoridWoo, NWS=36115531000en_HK
dc.identifier.scopusauthoridTam, KF=7201692816en_HK
dc.identifier.scopusauthoridNgan, HYS=34571944100en_HK
dc.identifier.scopusauthoridChan, QKY=8390404100en_HK
dc.identifier.scopusauthoridChan, DCW=34767736800en_HK
dc.identifier.scopusauthoridChan, KYK=7406034195en_HK
dc.identifier.scopusauthoridCheung, ANY=54927484100en_HK

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