Article: Overexpression of dedicator of cytokinesis I (Dock180) in ovarian cancer correlated with aggressive phenotype and poor patient survival
| Title | Overexpression of dedicator of cytokinesis I (Dock180) in ovarian cancer correlated with aggressive phenotype and poor patient survival | ||||||
|---|---|---|---|---|---|---|---|
| Authors | Zhao, F1 Siu, MKY1 Jiang, L1 Tam, KF1 Ngan, HYS1 Le, XF2 Wong, OGW1 Wong, ESY1 Chan, HY1 Cheung, ANY1 | ||||||
| Keywords | Dock180 expression Metastasis Ovarian cancer Prognostic factor | ||||||
| Issue Date | 2011 | ||||||
| Publisher | Blackwell Publishing Ltd. The Journal's web site is located at http://www.blackwellpublishing.com/journals/HIS | ||||||
| Citation | Histopathology, 2011, v. 59 n. 6, p. 1163-1172 [How to Cite?] DOI: http://dx.doi.org/10.1111/j.1365-2559.2011.04045.x | ||||||
| Abstract | Aims: Dedicator of cytokinesis I (Dock180) is a novel guanine nucleotide exchange factor for Rho guanosine triphosphates (GTPases) important for cell migration. The aim of this study was to evaluate the role of Dock180 in ovarian carcinogenesis. Methods and results: Using immunohistochemistry, real-time polymerase chain reaction and Western blotting, overexpression of Dock180 RNA and protein was demonstrated in the nucleus and cytoplasm of ovarian cancer cell lines (n=5) and clinical samples of ovarian borderline tumours (n=21) and invasive cancers (n=108) when compared with ovarian epithelial cell lines (n=3) and benign cystadenomas (n=10) (P<0.05). High Dock180 cytoplasmic expression in ovarian cancer (n=108) was associated significantly with serous histological type, high-grade cancer and advanced stage (P<0.05), as well as poor overall and disease-free survival (P=0.004). Using multivariate progression analysis, high Dock180 cytoplasmic expression and advanced cancer stage were found to be independent prognostic factors for short overall survival and disease-free survival (P<0.05). Exogenous expression of Dock180 by transient transfection enhanced cancer cell migration and invasion, whereas knockdown of Dock180 by an siRNA approach retarded cancer cell migration and invasion in association with down-regulation of matrix metalloproteinase 2. Conclusions: Our findings suggest that Dock180 contributes to ovarian carcinogenesis and dissemination and is a potential prognostic marker and therapeutic target. © 2011 Blackwell Publishing Limited. | ||||||
| ISSN | 0309-0167 2011 Impact Factor: 3.082 2011 SCImago Journal Rankings: 0.320 | ||||||
| DOI | http://dx.doi.org/10.1111/j.1365-2559.2011.04045.x | ||||||
| ISI Accession Number ID | WOS:000298358000014
Funding Information: The pCAGGS-Dock180 and control vector were kind gifts from Dr Jun-ichi Miyasaki (Osaka University, Osaka, Japan). This study was supported by funding from the Research Grants Council of the Hong Kong Special Administrative Region (HKU 7503/06M) and Hong Kong Anti-Cancer Society Fund. | ||||||
| References | References in Scopus | ||||||
| Grants | Akt and p21-activated kinase signaling pathways in gestational trophoblastic disease |
| dc.contributor.author | Zhao, F | ||||||
|---|---|---|---|---|---|---|---|
| dc.contributor.author | Siu, MKY | ||||||
| dc.contributor.author | Jiang, L | ||||||
| dc.contributor.author | Tam, KF | ||||||
| dc.contributor.author | Ngan, HYS | ||||||
| dc.contributor.author | Le, XF | ||||||
| dc.contributor.author | Wong, OGW | ||||||
| dc.contributor.author | Wong, ESY | ||||||
| dc.contributor.author | Chan, HY | ||||||
| dc.contributor.author | Cheung, ANY | ||||||
| dc.date.accessioned | 2012-05-29T06:14:37Z | ||||||
| dc.date.available | 2012-05-29T06:14:37Z | ||||||
| dc.date.issued | 2011 | ||||||
| dc.description.abstract | Aims: Dedicator of cytokinesis I (Dock180) is a novel guanine nucleotide exchange factor for Rho guanosine triphosphates (GTPases) important for cell migration. The aim of this study was to evaluate the role of Dock180 in ovarian carcinogenesis. Methods and results: Using immunohistochemistry, real-time polymerase chain reaction and Western blotting, overexpression of Dock180 RNA and protein was demonstrated in the nucleus and cytoplasm of ovarian cancer cell lines (n=5) and clinical samples of ovarian borderline tumours (n=21) and invasive cancers (n=108) when compared with ovarian epithelial cell lines (n=3) and benign cystadenomas (n=10) (P<0.05). High Dock180 cytoplasmic expression in ovarian cancer (n=108) was associated significantly with serous histological type, high-grade cancer and advanced stage (P<0.05), as well as poor overall and disease-free survival (P=0.004). Using multivariate progression analysis, high Dock180 cytoplasmic expression and advanced cancer stage were found to be independent prognostic factors for short overall survival and disease-free survival (P<0.05). Exogenous expression of Dock180 by transient transfection enhanced cancer cell migration and invasion, whereas knockdown of Dock180 by an siRNA approach retarded cancer cell migration and invasion in association with down-regulation of matrix metalloproteinase 2. Conclusions: Our findings suggest that Dock180 contributes to ovarian carcinogenesis and dissemination and is a potential prognostic marker and therapeutic target. © 2011 Blackwell Publishing Limited. | ||||||
| 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 | Histopathology, 2011, v. 59 n. 6, p. 1163-1172 [How to Cite?] DOI: http://dx.doi.org/10.1111/j.1365-2559.2011.04045.x | ||||||
| dc.identifier.doi | http://dx.doi.org/10.1111/j.1365-2559.2011.04045.x | ||||||
| dc.identifier.epage | 1172 | ||||||
| dc.identifier.hkuros | 211340 | ||||||
| dc.identifier.isi | WOS:000298358000014
Funding Information: The pCAGGS-Dock180 and control vector were kind gifts from Dr Jun-ichi Miyasaki (Osaka University, Osaka, Japan). This study was supported by funding from the Research Grants Council of the Hong Kong Special Administrative Region (HKU 7503/06M) and Hong Kong Anti-Cancer Society Fund. | ||||||
| dc.identifier.issn | 0309-0167 2011 Impact Factor: 3.082 2011 SCImago Journal Rankings: 0.320 | ||||||
| dc.identifier.issue | 6 | ||||||
| dc.identifier.pmid | 22175896 | ||||||
| dc.identifier.scopus | eid_2-s2.0-84855926182 | ||||||
| dc.identifier.spage | 1163 | ||||||
| dc.identifier.uri | http://hdl.handle.net/10722/148679 | ||||||
| dc.identifier.volume | 59 | ||||||
| dc.language | eng | ||||||
| dc.publisher | Blackwell Publishing Ltd. The Journal's web site is located at http://www.blackwellpublishing.com/journals/HIS | ||||||
| dc.publisher.place | United Kingdom | ||||||
| dc.relation.ispartof | Histopathology | ||||||
| dc.relation.references | References in Scopus | ||||||
| dc.subject.mesh | Adult | ||||||
| dc.subject.mesh | Aged | ||||||
| dc.subject.mesh | Aged, 80 And Over | ||||||
| dc.subject.mesh | Blotting, Western | ||||||
| dc.subject.mesh | Carcinoma - Enzymology - Mortality - Pathology | ||||||
| dc.subject.mesh | Cell Movement - Genetics | ||||||
| dc.subject.mesh | Cystadenoma - Enzymology - Mortality - Pathology | ||||||
| dc.subject.mesh | Female | ||||||
| dc.subject.mesh | Humans | ||||||
| dc.subject.mesh | Immunohistochemistry | ||||||
| dc.subject.mesh | Microscopy, Confocal | ||||||
| dc.subject.mesh | Middle Aged | ||||||
| dc.subject.mesh | Neoplasm Grading | ||||||
| dc.subject.mesh | Neoplasm Invasiveness - Genetics - Pathology | ||||||
| dc.subject.mesh | Ovarian Neoplasms - Enzymology - Mortality - Pathology | ||||||
| dc.subject.mesh | Phenotype | ||||||
| dc.subject.mesh | Prognosis | ||||||
| dc.subject.mesh | Rna, Small Interfering | ||||||
| dc.subject.mesh | Real-Time Polymerase Chain Reaction | ||||||
| dc.subject.mesh | Reverse Transcriptase Polymerase Chain Reaction | ||||||
| dc.subject.mesh | Transfection | ||||||
| dc.subject.mesh | Tumor Markers, Biological - Analysis | ||||||
| dc.subject.mesh | Up-Regulation | ||||||
| dc.subject.mesh | Young Adult | ||||||
| dc.subject.mesh | Rac Gtp-Binding Proteins - Analysis - Biosynthesis | ||||||
| dc.subject | Dock180 expression | ||||||
| dc.subject | Metastasis | ||||||
| dc.subject | Ovarian cancer | ||||||
| dc.subject | Prognostic factor | ||||||
| dc.title | Overexpression of dedicator of cytokinesis I (Dock180) in ovarian cancer correlated with aggressive phenotype and poor patient survival | ||||||
| dc.type | Article |
Author Affiliations
- The University of Hong Kong
- University of Texas M. D. Anderson Cancer Center