Journal article
Biological Significance of Focal Adhesion Kinase in Ovarian Cancer: Role in Migration and Invasion
The American journal of pathology, Vol.165(4), pp.1087-1095
10/2004
DOI: 10.1016/S0002-9440(10)63370-6
PMCID: PMC1618649
PMID: 15466376
Abstract
Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase that is activated by integrin clustering. There are limited data regarding the functional role of FAK in ovarian cancer migration and invasion. In the current study, FAK expression was evaluated in ovarian cell lines (nontransformed and cancer), 12 benign ovarian samples, and in 79 invasive epithelial ovarian cancers. All three ovarian cancer cell lines overexpressed FAK compared to the nontransformed cells. The dominant-negative construct called FAK-related nonkinase (FRNK) was introduced into two ovarian cancer cell lines (SKOV3 and 222). FRNK promoted FAK dephosphorylation without changing total FAK levels in these cell lines. Furthermore, FRNK decreased the
in vitro
invasive ability of ovarian cancer cells by 56 to 85% and decreased migration by 52 to 68%. FRNK-transfected cells also displayed poor cell spreading. Immunohistochemical analysis revealed that the surface epithelium from all benign ovarian samples had weak FAK expression. In contrast, 68% of invasive ovarian cancers overexpressed FAK. FAK overexpression was significantly associated with high tumor stage, high tumor grade, positive lymph nodes and presence of distant metastasis (all
P
values <0.05). FAK overexpression was also associated with shorter overall survival (
P
= 0.008). Multivariate analysis revealed that FAK overexpression and residual disease >1 cm were independent predictors of poor survival. These data indicate that FAK is overexpressed in most invasive ovarian cancers and plays a functionally significant role in ovarian cancer migration and invasion. Thus, FAK may be an important therapeutic target in ovarian carcinoma.
Details
- Title: Subtitle
- Biological Significance of Focal Adhesion Kinase in Ovarian Cancer: Role in Migration and Invasion
- Creators
- Anil K Sood - From the Department of Gynecologic OncologyJeremy E Coffin - From the Department of Gynecologic OncologyGalen B Schneider - From the Department of Gynecologic OncologyMavis S Fletcher - From the Department of Gynecologic OncologyBarry R DeYoung - From the Department of Gynecologic OncologyLynn M Gruman - From the Department of Gynecologic OncologyDavid M Gershenson - From the Department of Gynecologic OncologyMichael D Schaller - From the Department of Gynecologic OncologyMary J.C Hendrix - From the Department of Gynecologic Oncology
- Resource Type
- Journal article
- Publication Details
- The American journal of pathology, Vol.165(4), pp.1087-1095
- Publisher
- American Society for Investigative Pathology
- DOI
- 10.1016/S0002-9440(10)63370-6
- PMID
- 15466376
- PMCID
- PMC1618649
- ISSN
- 0002-9440
- eISSN
- 1525-2191
- Language
- English
- Date published
- 10/2004
- Academic Unit
- Dentistry Administration; Prosthodontics
- Record Identifier
- 9984065708502771
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