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BMC Cancer
Published in: BMC Cancer 1/2014

Open Access 01-12-2014 | Research article

High focal adhesion kinase expression in breast carcinoma is associated with lymphovascular invasion and triple-negative phenotype

Authors: Vita M Golubovskaya, Lourdes Ylagan, Austin Miller, Melissa Hughes, Jason Wilson, David Wang, Elizabeth Brese, Wiam Bshara, Stephen Edge, Carl Morrison, William G Cance

Published in: BMC Cancer | Issue 1/2014

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Abstract

Background

Focal adhesion Kinase (FAK) is a nonreceptor protein tyrosine kinase that is overexpressed in tumors and plays a significant role in tumor survival and metastasis. The purpose of the study is to perform correlation of FAK expression with patient prognostic factors using tissue microarrays (TMA) samples.

Methods

We analyzed FAK expression by immunohistochemical staining in 196 breast primary tumor samples from stage II-IV patients and in 117 metastatic tissues matched to the primary tumors using TMA that were stained with FAK monoclonal antibody.

Results

High FAK expression in primary tumors was associated with a younger age of patients (p = 0.033), lymphovascular invasion (p = 0.001) and with the triple-negative phenotype (p = 0.033). FAK expression in 117 metastatic tissues positively correlated with FAK expression in matched primary tumors by Spearman correlation analysis. In addition, a strong positive correlation was observed between high FAK expression and shorter overall survival and progression free survival in patients with metastatic tumors.

Conclusions

The data demonstrate a high potential for FAK as a therapeutic target, especially in triple-negative breast cancer patients with high FAK expression.
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Literature
1.
Cance WG, Golubovskaya VM: Focal adhesion kinase versus p53: apoptosis or survival?. Sci Signal. 2008, 1 (20): e22-CrossRef
2.
Gabarra-Niecko V, Schaller MD, Dunty JM: FAK regulates biological processes important for the pathogenesis of cancer. Cancer Metastasis Rev. 2003, 22 (4): 359-374. 10.1023/A:1023725029589.CrossRefPubMed
3.
Frame MC, Patel H, Serrels B, Lietha D, Eck MJ: The FERM domain: organizing the structure and function of FAK. Nat Rev Mol Cell Biol. 2010, 11 (11): 802-814. 10.1038/nrm2996.CrossRefPubMed
4.
Lark AL, Livasy CA, Calvo B, Caskey L, Moore DT, Yang X, Cance WG: Overexpression of focal adhesion kinase in primary colorectal carcinomas and colorectal liver metastases: immunohistochemistry and real-time PCR analyses. Clin Cancer Res. 2003, 9 (1): 215-222.PubMed
5.
Owens LV, Xu L, Dent GA, Yang X, Sturge GC, Craven RJ, Cance WG: Focal adhesion kinase as a marker of invasive potential in differentiated human thyroid cancer. Ann Surg Oncol. 1996, 3 (1): 100-105. 10.1007/BF02409059.CrossRefPubMed
6.
Hochwald SN, Nyberg C, Zheng M, Zheng D, Wood C, Massoll NA, Magis A, Ostrov D, Cance WG, Golubovskaya VM: A novel small molecule inhibitor of FAK decreases growth of human pancreatic cancer. Cell Cycle. 2009, 8 (15): 2435-2443. 10.4161/cc.8.15.9145.CrossRefPubMedPubMedCentral
7.
Judson PL, He X, Cance WG, Van Le L: Overexpression of focal adhesion kinase, a protein tyrosine kinase, in ovarian carcinoma. Cancer. 1999, 86 (8): 1551-1556. 10.1002/(SICI)1097-0142(19991015)86:6<1551::AID-CNCR23>3.0.CO;2-P.CrossRefPubMed
8.
Hecker TP, Grammer JR, Gillespie GY, Stewart J, Gladson CL: Focal adhesion kinase enhances signaling through the Shc/extracellular signal-regulated kinase pathway in anaplastic astrocytoma tumor biopsy samples. Cancer Res. 2002, 62 (9): 2699-2707.PubMed
9.
Beierle EA, Massoll NA, Hartwich J, Kurenova EV, Golubovskaya VM, Cance WG, McGrady P, London WB: Focal adhesion kinase expression in human neuroblastoma: immunohistochemical and real-time PCR analyses. Clin Cancer Res. 2008, 14 (11): 3299-3305. 10.1158/1078-0432.CCR-07-1511.CrossRefPubMed
10.
Kornberg LJ: Focal adhesion kinase expression in oral cancers. Head Neck. 1998, 20 (7): 634-639. 10.1002/(SICI)1097-0347(199810)20:7<634::AID-HED10>3.0.CO;2-M.CrossRefPubMed
11.
Lark AL, Livasy CA, Dressler L, Moore DT, Millikan RC, Geradts J, Iacocca M, Cowan D, Little D, Craven RJ, Cance W: High focal adhesion kinase expression in invasive breast carcinomas is associated with an aggressive phenotype. Mod Pathol. 2005, 18 (10): 1289-1294. 10.1038/modpathol.3800424.CrossRefPubMed
12.
Lightfoot HM, Lark A, Livasy CA, Moore DT, Cowan D, Dressler L, Craven RJ, Cance WG: Upregulation of focal adhesion kinase (FAK) expression in ductal carcinoma in situ (DCIS) is an early event in breast tumorigenesis. Breast Cancer Res Treat. 2004, 88 (2): 109-116. 10.1007/s10549-004-1022-8.CrossRefPubMed
13.
Kononen J, Bubendorf L, Kallioniemi A, Barlund M, Schraml P, Leighton S, Torhorst J, Mihatsch MJ, Sauter G, Kallioniemi OP: Tissue microarrays for high-throughput molecular profiling of tumor specimens. Nat Med. 1998, 4 (7): 844-847. 10.1038/nm0798-844.CrossRefPubMed
14.
Allred DC, Harvey JM, Berardo M, Clark GM: Prognostic and predictive factors in breast cancer by immunohistochemical analysis. Mod Pathol. 1998, 11 (2): 155-168.PubMed
15.
Sheen-Chen SM, Huang CY, Chan YC, Tsai CH, Chi SY, Wu SC, Huang CC, Tang RP, Eng HL, Ko SF, Lee YW, Liang JL, Huang EY, Chen HC, Rau KM: An evaluation of focal adhesion kinase in breast cancer by tissue microarrays. Anticancer Res. 2013, 33 (3): 1169-1173.PubMed
16.
Benlimame N, He Q, Jie S, Xiao D, Xu YJ, Loignon M, Schlaepfer DD, Alaoui-Jamali MA: FAK signaling is critical for ErbB-2/ErbB-3 receptor cooperation for oncogenic transformation and invasion. J Cell Biol. 2005, 171 (3): 505-516. 10.1083/jcb.200504124.CrossRefPubMedPubMedCentral
17.
Lazaro G, Smith C, Goddard L, Jordan N, McClelland R, Barrett-Lee P, Nicholson RI, Hiscox S: Targeting focal adhesion kinase in ER+/HER2+ breast cancer improves trastuzumab response. Endocr Relat Cancer. 2013, 20 (5): 691-704. 10.1530/ERC-13-0019.CrossRefPubMed
18.
Yom CK, Noh DY, Kim WH, Kim HS: Clinical significance of high focal adhesion kinase gene copy number and overexpression in invasive breast cancer. Breast Cancer Res Treat. 2011, 128 (3): 647-655. 10.1007/s10549-010-1150-2.CrossRefPubMed
19.
Engebraaten O, Vollan HK, Borresen-Dale AL: Triple-negative breast cancer and the need for new therapeutic targets. Am J Pathol. 2013, 183 (4): 1064-1074. 10.1016/j.ajpath.2013.05.033.CrossRefPubMed
20.
Golubovskaya VM, Nyberg C, Zheng M, Kweh F, Magis A, Ostrov D, Cance WG: A small molecule inhibitor, 1,2,4,5-benzenetetraamine tetrahydrochloride, targeting the Y397 site of focal adhesion kinase decreases tumor growth. J Med Chem. 2008, 51: 7405-7416. 10.1021/jm800483v.CrossRefPubMedPubMedCentral
21.
Beierle EA, Ma X, Trujillo A, Kurenova EV, Cance WG, Golubovskaya VM: Inhibition of focal adhesion kinase and src increases detachment and apoptosis in human neuroblastoma cell lines. Mol Carcinog. 2010, 49: 224-234.PubMedPubMedCentral
22.
Cance WG, Kurenova E, Marlowe T, Golubovskaya V: Disrupting the scaffold to improve focal adhesion kinase-targeted cancer therapeutics. Sci Signal. 2013, 6 (268): e10-CrossRef
23.
Frisch SM, Schaller M, Cieply B: Mechanisms that link the oncogenic epithelial-mesenchymal transition to suppression of anoikis. J Cell Sci. 2013, 126 (Pt 1): 21-29.CrossRefPubMedPubMedCentral
24.
Lechertier T, Hodivala-Dilke K: Focal adhesion kinase and tumour angiogenesis. J Pathol. 2012, 226 (2): 404-412. 10.1002/path.3018.CrossRefPubMed
25.
Shibue T, Weinberg RA: Integrin beta1-focal adhesion kinase signaling directs the proliferation of metastatic cancer cells disseminated in the lungs. Proc Natl Acad Sci U S A. 2009, 106 (25): 10290-10295. 10.1073/pnas.0904227106.CrossRefPubMedPubMedCentral
26.
Skobe M, Hawighorst T, Jackson DG, Prevo R, Janes L, Velasco P, Riccardi L, Alitalo K, Claffey K, Detmar M: Induction of tumor lymphangiogenesis by VEGF-C promotes breast cancer metastasis. Nat Med. 2001, 7 (2): 192-198. 10.1038/84643.CrossRefPubMed
27.
Rakha EA, Martin S, Lee AH, Morgan D, Pharoah PD, Hodi Z, Macmillan D, Ellis IO: The prognostic significance of lymphovascular invasion in invasive breast carcinoma. Cancer. 2012, 118 (15): 3670-3680. 10.1002/cncr.26711.CrossRefPubMed
Metadata
Title
High focal adhesion kinase expression in breast carcinoma is associated with lymphovascular invasion and triple-negative phenotype
Authors
Vita M Golubovskaya
Lourdes Ylagan
Austin Miller
Melissa Hughes
Jason Wilson
David Wang
Elizabeth Brese
Wiam Bshara
Stephen Edge
Carl Morrison
William G Cance
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2014
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-14-769

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