Expression and Clinical Significance of FAK and Src Proteins in Human Endometrial Adenocarcinoma

Overview

Journal Pathol Oncol Res

Specialty Oncology

Date 2010 Nov 9

PMID 21058027

Citations 1

Authors

Nikolaos A Chatzizacharias

Constantinos Giaginis

Elisavet Gatzidou

Gerasimos Tsourouflis

Ioannis Sfiniadakis

Paraskevi Alexandrou

Stamatios E Theocharis

Affiliations

Soon will be listed here.

Abstract

Focal Adhesion Kinase (FAK) is a protein tyrosine kinase, localised in the focal adhesions, which, upon activation interacts with Src, another tyrosine kinase, regulating several cellular signalling pathways. Both enzymes have been implicated in malignant transformation and disease progression. The aim of the present study was to evaluate the clinical significance of FAK and Src expression in cases of endometrial adenocarcinoma. The total (t) and the activated, phosphorylated (p) forms of FAK and Src proteins were assessed immunohistochemically in tumour specimens obtained from 43 endometrial adenocarcinoma patients and were statistically analyzed in relation to various clinicopathological parameters and tumour proliferative capacity, reflected by Ki-67 labelling index. t-FAK positivity was significantly correlated with FIGO disease stage (p = 0.031), and t-FAK overexpression with patients' age (p = 0.015). No statistically significant correlation was identified between t-FAK staining intensity, t-Src positivity, overexpression or staining intensity and any of the clinicopathological parameters tested. No significant correlation was found between neither the positivity nor the intensity of staining of either p-FAk or p-Src with any of the parameters under study. Nonetheless, important, but non-significant, trends were identified between t-FAK staining intensity, t-Src positivity and overexpression and patients' survival (log rank, p = 0.122, p = 0.090 and p = 0.057 respectively). Similarly, p-FAK and p-Src staining characteristics seemed to correlate, even though non-significantly, with patients' survival (log rank, p = 0.051 and p = 0.070 for p-FAK and p-Src expression, respectively; log rank, p = 0.134 and p = 0.110 for p-FAK and p-Src staining intensity, respectively). These results support an important potential role of FAK-Src signalling in endometrial malignant disease progress and render further research in this field a necessity.

Citing Articles

FAK and Src expression in mobile tongue squamous cell carcinoma: associations with clinicopathological parameters and patients survival.

Theocharis S, Klijanienko J, Giaginis C, Alexandrou P, Patsouris E, Sastre-Garau X J Cancer Res Clin Oncol. 2012; 138(8):1369-77.

PMID: 22488171 DOI: 10.1007/s00432-012-1215-1.

References

Chatzizacharias N, Giaginis C, Zizi-Serbetzoglou D, Kouraklis G, Karatzas G, Theocharis S . Evaluation of the clinical significance of focal adhesion kinase and SRC expression in human pancreatic ductal adenocarcinoma. Pancreas. 2010; 39(6):930-6. DOI: 10.1097/MPA.0b013e3181d7abcc. View

Myoui A, Nishimura R, Williams P, Hiraga T, Tamura D, Michigami T . C-SRC tyrosine kinase activity is associated with tumor colonization in bone and lung in an animal model of human breast cancer metastasis. Cancer Res. 2003; 63(16):5028-33. View

Xing Z, Chen H, Nowlen J, Taylor S, Shalloway D, Guan J . Direct interaction of v-Src with the focal adhesion kinase mediated by the Src SH2 domain. Mol Biol Cell. 1994; 5(4):413-21. PMC: 301051. DOI: 10.1091/mbc.5.4.413. View

Sorenson C, Sheibani N . Focal adhesion kinase, paxillin, and bcl-2: analysis of expression, phosphorylation, and association during morphogenesis. Dev Dyn. 1999; 215(4):371-82. DOI: 10.1002/(SICI)1097-0177(199908)215:4<371::AID-AJA8>3.0.CO;2-H. View

Ito H, Gardner-Thorpe J, Zinner M, Ashley S, Whang E . Inhibition of tyrosine kinase Src suppresses pancreatic cancer invasiveness. Surgery. 2003; 134(2):221-6. DOI: 10.1067/msy.2003.224. View

Schaller M, Parsons J . Focal adhesion kinase and associated proteins. Curr Opin Cell Biol. 1994; 6(5):705-10. DOI: 10.1016/0955-0674(94)90097-3. View

Lutz M, Esser I, Vogelmann R, Luhrs H, Friess H, Buchler M . Overexpression and activation of the tyrosine kinase Src in human pancreatic carcinoma. Biochem Biophys Res Commun. 1998; 243(2):503-8. DOI: 10.1006/bbrc.1997.8043. View

Su J, Gui L, Zhou Y, Zha X . Expression of focal adhesion kinase and alpha5 and beta1 integrins in carcinomas and its clinical significance. World J Gastroenterol. 2002; 8(4):613-8. PMC: 4656308. DOI: 10.3748/wjg.v8.i4.613. View

Hauck C, Hunter T, Schlaepfer D . The v-Src SH3 domain facilitates a cell adhesion-independent association with focal adhesion kinase. J Biol Chem. 2001; 276(21):17653-62. DOI: 10.1074/jbc.M009329200. View

10.

Hanks S, Calalb M, Harper M, Patel S . Focal adhesion protein-tyrosine kinase phosphorylated in response to cell attachment to fibronectin. Proc Natl Acad Sci U S A. 1992; 89(18):8487-91. PMC: 49945. DOI: 10.1073/pnas.89.18.8487. View

11.

CARY L, Guan J . Focal adhesion kinase in integrin-mediated signaling. Front Biosci. 1999; 4:D102-13. DOI: 10.2741/cary. View

12.

Lipfert L, Haimovich B, Schaller M, Cobb B, Parsons J, Brugge J . Integrin-dependent phosphorylation and activation of the protein tyrosine kinase pp125FAK in platelets. J Cell Biol. 1992; 119(4):905-12. PMC: 2289696. DOI: 10.1083/jcb.119.4.905. View

13.

MacPhee D, Mostachfi H, Han R, Lye S, Post M, Caniggia I . Focal adhesion kinase is a key mediator of human trophoblast development. Lab Invest. 2001; 81(11):1469-83. DOI: 10.1038/labinvest.3780362. View

14.

Shen T, Park A, Alcaraz A, Peng X, Jang I, Koni P . Conditional knockout of focal adhesion kinase in endothelial cells reveals its role in angiogenesis and vascular development in late embryogenesis. J Cell Biol. 2005; 169(6):941-52. PMC: 2171636. DOI: 10.1083/jcb.200411155. View

15.

Cox B, Natarajan M, Stettner M, Gladson C . New concepts regarding focal adhesion kinase promotion of cell migration and proliferation. J Cell Biochem. 2006; 99(1):35-52. DOI: 10.1002/jcb.20956. View

16.

Chatzizacharias N, Kouraklis G, Theocharis S . Clinical significance of FAK expression in human neoplasia. Histol Histopathol. 2008; 23(5):629-50. DOI: 10.14670/HH-23.629. View

17.

Guan J, Shalloway D . Regulation of focal adhesion-associated protein tyrosine kinase by both cellular adhesion and oncogenic transformation. Nature. 1992; 358(6388):690-2. DOI: 10.1038/358690a0. View

18.

Verbeek B, Vroom T, Geertzema J, Hennipman A, Rijksen G . c-Src protein expression is increased in human breast cancer. An immunohistochemical and biochemical analysis. J Pathol. 1996; 180(4):383-8. DOI: 10.1002/(SICI)1096-9896(199612)180:4<383::AID-PATH686>3.0.CO;2-N. View

19.

Schlaepfer D, Hauck C, Sieg D . Signaling through focal adhesion kinase. Prog Biophys Mol Biol. 1999; 71(3-4):435-78. DOI: 10.1016/s0079-6107(98)00052-2. View

20.

Salasznyk R, Klees R, Williams W, Boskey A, Plopper G . Focal adhesion kinase signaling pathways regulate the osteogenic differentiation of human mesenchymal stem cells. Exp Cell Res. 2006; 313(1):22-37. PMC: 1780174. DOI: 10.1016/j.yexcr.2006.09.013. View