Article: Differential expression and phosphorylation of Pak1 and Pak2 in ovarian cancer: Effects on prognosis and cell invasion
File Download
(May Require Subscription)
- No File Attached
(May Require Subscription)
- Publisher Website: 10.1002/ijc.25005
- Scopus: eid_2-s2.0-77953465926
- PMID: 19876919
- Find via
Supplementary
-
Citations:
-
Appears in Collections:
| Title | Differential expression and phosphorylation of Pak1 and Pak2 in ovarian cancer: Effects on prognosis and cell invasion | ||||||
|---|---|---|---|---|---|---|---|
| Authors | Siu, MKY1 Wong, ESY1 Chan, HY1 Kong, DSH1 Woo, NWS1 Tam, KF1 Ngan, HYS1 Chan, QKY1 Chan, DCW1 Chan, KYK1 Cheung, ANY1 | ||||||
| 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?] DOI: http://dx.doi.org/10.1002/ijc.25005 | ||||||
| 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. | ||||||
| ISSN | 0020-7136 2011 Impact Factor: 5.444 2011 SCImago Journal Rankings: 0.620 | ||||||
| DOI | http://dx.doi.org/10.1002/ijc.25005 | ||||||
| ISI Accession Number ID | WOS:000278148800003
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 | References in Scopus | ||||||
| Grants | Akt and p21-activated kinase signaling pathways in gestational trophoblastic disease |
| dc.contributor.author | Siu, MKY | ||||||
|---|---|---|---|---|---|---|---|
| dc.contributor.author | Wong, ESY | ||||||
| dc.contributor.author | Chan, HY | ||||||
| dc.contributor.author | Kong, DSH | ||||||
| dc.contributor.author | Woo, NWS | ||||||
| dc.contributor.author | Tam, KF | ||||||
| dc.contributor.author | Ngan, HYS | ||||||
| dc.contributor.author | Chan, QKY | ||||||
| dc.contributor.author | Chan, DCW | ||||||
| dc.contributor.author | Chan, KYK | ||||||
| dc.contributor.author | Cheung, ANY | ||||||
| dc.date.accessioned | 2010-10-31T12:44:25Z | ||||||
| dc.date.available | 2010-10-31T12:44:25Z | ||||||
| dc.date.issued | 2010 | ||||||
| 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. | ||||||
| dc.description.grant | Akt and p21-activated kinase signaling pathways in gestational trophoblastic disease | ||||||
| dc.description.grantcode | 82405 | ||||||
| dc.description.nature | Link_to_subscribed_fulltext | ||||||
| dc.identifier.citation | International 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.doi | http://dx.doi.org/10.1002/ijc.25005 | ||||||
| dc.identifier.epage | 31 | ||||||
| dc.identifier.hkuros | 174761 | ||||||
| dc.identifier.isi | WOS:000278148800003
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.issn | 0020-7136 2011 Impact Factor: 5.444 2011 SCImago Journal Rankings: 0.620 | ||||||
| dc.identifier.issue | 1 | ||||||
| dc.identifier.openurl | | ||||||
| dc.identifier.pmid | 19876919 | ||||||
| dc.identifier.scopus | eid_2-s2.0-77953465926 | ||||||
| dc.identifier.spage | 21 | ||||||
| dc.identifier.uri | http://hdl.handle.net/10722/126717 | ||||||
| dc.identifier.volume | 127 | ||||||
| dc.language | eng | ||||||
| dc.publisher | John Wiley & Sons, Inc.. The Journal's web site is located at http://www3.interscience.wiley.com/journal/29331/home | ||||||
| dc.publisher.place | United States | ||||||
| dc.relation.ispartof | International Journal of Cancer | ||||||
| dc.relation.references | References in Scopus | ||||||
| dc.subject.mesh | Apoptosis | ||||||
| dc.subject.mesh | Base Sequence | ||||||
| dc.subject.mesh | Blotting, Western | ||||||
| dc.subject | Cell invasion | ||||||
| dc.subject | Ovarian cancer | ||||||
| dc.subject | Pak1 | ||||||
| dc.subject | Pak2 | ||||||
| dc.subject | Phosphorylation | ||||||
| dc.subject | Prognosis | ||||||
| dc.title | Differential expression and phosphorylation of Pak1 and Pak2 in ovarian cancer: Effects on prognosis and cell invasion | ||||||
| dc.type | Article |
Author Affiliations
- The University of Hong Kong