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Article: Differential expression and phosphorylation of Pak1 and Pak2 in ovarian cancer: Effects on prognosis and cell invasion
Title | Differential expression and phosphorylation of Pak1 and Pak2 in ovarian cancer: Effects on prognosis and cell invasion | ||||||
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Authors | |||||||
Keywords | Cell invasion Ovarian cancer Pak1 Pak2 Phosphorylation Prognosis | ||||||
Issue Date | 2010 | ||||||
Publisher | John 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 Identifier | http://hdl.handle.net/10722/126717 | ||||||
ISSN | 2023 Impact Factor: 5.7 2023 SCImago Journal Rankings: 2.131 | ||||||
ISI Accession Number ID |
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 |
DC Field | Value | Language |
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dc.contributor.author | Siu, MKY | en_HK |
dc.contributor.author | Wong, ESY | en_HK |
dc.contributor.author | Chan, HY | en_HK |
dc.contributor.author | Kong, DSH | en_HK |
dc.contributor.author | Woo, NWS | en_HK |
dc.contributor.author | Tam, KF | en_HK |
dc.contributor.author | Ngan, HYS | en_HK |
dc.contributor.author | Chan, QKY | en_HK |
dc.contributor.author | Chan, DCW | en_HK |
dc.contributor.author | Chan, KYK | en_HK |
dc.contributor.author | Cheung, ANY | en_HK |
dc.date.accessioned | 2010-10-31T12:44:25Z | - |
dc.date.available | 2010-10-31T12:44:25Z | - |
dc.date.issued | 2010 | en_HK |
dc.identifier.citation | International Journal Of Cancer, 2010, v. 127 n. 1, p. 21-31 | en_HK |
dc.identifier.issn | 0020-7136 | en_HK |
dc.identifier.uri | http://hdl.handle.net/10722/126717 | - |
dc.description.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. | en_HK |
dc.language | eng | en_HK |
dc.publisher | John Wiley & Sons, Inc.. The Journal's web site is located at http://www3.interscience.wiley.com/journal/29331/home | en_HK |
dc.relation.ispartof | International Journal of Cancer | en_HK |
dc.subject | Cell invasion | en_HK |
dc.subject | Ovarian cancer | en_HK |
dc.subject | Pak1 | en_HK |
dc.subject | Pak2 | en_HK |
dc.subject | Phosphorylation | en_HK |
dc.subject | Prognosis | en_HK |
dc.subject.mesh | Apoptosis | - |
dc.subject.mesh | Base Sequence | - |
dc.subject.mesh | Blotting, Western | - |
dc.title | Differential expression and phosphorylation of Pak1 and Pak2 in ovarian cancer: Effects on prognosis and cell invasion | en_HK |
dc.type | Article | en_HK |
dc.identifier.openurl | http://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+invasion | en_HK |
dc.identifier.email | Siu, MKY: mkysiu@hkucc.hku.hk | en_HK |
dc.identifier.email | Ngan, HYS: hysngan@hkucc.hku.hk | en_HK |
dc.identifier.email | Chan, KYK: kelvinc@pathology.hku.hk | en_HK |
dc.identifier.email | Cheung, ANY: anycheun@hkucc.hku.hk | en_HK |
dc.identifier.authority | Siu, MKY=rp00275 | en_HK |
dc.identifier.authority | Ngan, HYS=rp00346 | en_HK |
dc.identifier.authority | Chan, KYK=rp00453 | en_HK |
dc.identifier.authority | Cheung, ANY=rp00542 | en_HK |
dc.description.nature | link_to_subscribed_fulltext | - |
dc.identifier.doi | 10.1002/ijc.25005 | en_HK |
dc.identifier.pmid | 19876919 | en_HK |
dc.identifier.scopus | eid_2-s2.0-77953465926 | en_HK |
dc.identifier.hkuros | 174761 | en_HK |
dc.relation.references | http://www.scopus.com/mlt/select.url?eid=2-s2.0-77953465926&selection=ref&src=s&origin=recordpage | en_HK |
dc.identifier.volume | 127 | en_HK |
dc.identifier.issue | 1 | en_HK |
dc.identifier.spage | 21 | en_HK |
dc.identifier.epage | 31 | en_HK |
dc.identifier.isi | WOS:000278148800003 | - |
dc.publisher.place | United States | en_HK |
dc.relation.project | Akt and p21-activated kinase signaling pathways in gestational trophoblastic disease | - |
dc.identifier.scopusauthorid | Siu, MKY=24924018400 | en_HK |
dc.identifier.scopusauthorid | Wong, ESY=23101622300 | en_HK |
dc.identifier.scopusauthorid | Chan, HY=26024081600 | en_HK |
dc.identifier.scopusauthorid | Kong, DSH=36113859000 | en_HK |
dc.identifier.scopusauthorid | Woo, NWS=36115531000 | en_HK |
dc.identifier.scopusauthorid | Tam, KF=7201692816 | en_HK |
dc.identifier.scopusauthorid | Ngan, HYS=34571944100 | en_HK |
dc.identifier.scopusauthorid | Chan, QKY=8390404100 | en_HK |
dc.identifier.scopusauthorid | Chan, DCW=34767736800 | en_HK |
dc.identifier.scopusauthorid | Chan, KYK=7406034195 | en_HK |
dc.identifier.scopusauthorid | Cheung, ANY=54927484100 | en_HK |
dc.identifier.issnl | 0020-7136 | - |