Skip to main content

Advertisement

Log in

Overexpression of focal adhesion kinase correlates with increased lymph node metastasis and poor prognosis in non-small-cell lung cancer

  • Original Paper
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Background

The aim of this study was to investigate whether focal adhesion kinase (FAK) overexpression correlates with lymph node metastases and prognosis.

Methods

The protein expression of FAK was investigated in 153 paraffin-embedded tissues by immunohistochemical analysis and then correlated with various clinicopathologic parameters. FAK mRNA level was detected with quantitative RT-PCR in 57 NSCLC frozen tissues and 20 normal matched tissues.

Results

Immunohistochemistry showed FAK overexpression was significantly associated with positive lymph node metastasis and more advanced disease stage of NSCLCs and adenocarcinoma subtype; real-time PCR also indicated a statistically significant correlation between increased FAK mRNA level and the presence of nodal metastases. Moreover, in survival analysis, FAK overexpression was significantly associated with worse overall survival.

Conclusions

FAK overexpression is a promising pathological factor to predict aggressive behavior and prognosis in patients with NSCLC, particularly in the adenocarcinoma subtype.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Benlimame N, He Q, Jie S et al (2005) FAK signaling is critical for ErbB-2/ErbB-3 receptor cooperation for oncogenic transformation and invasion. J Cell Biol 171:505–516

    Article  PubMed  CAS  Google Scholar 

  • Brundage MD, Davies D, Mackillop WJ (2002) Prognostic factors in non-small cell lung cancer: a decade of prognosis. Chest 122:1037–1057

    Article  PubMed  Google Scholar 

  • Carelli S, Zadra G, Vaira V, et al (2006) Up-regulation of focal adhesion kinase in non-small cell lung cancer. Lung Cancer. 53(3):263–71

    Google Scholar 

  • Dunn KB, Heffler M, Golubovskaya VM (2010) Evolving therapies and FAK inhibitors for the treatment of cancer. Anticancer Agents Med Chem 10:722–734

    Article  PubMed  CAS  Google Scholar 

  • Evan G (2010) Getting one’s Fak straight. Dev Cell 19:185–186

    Article  PubMed  CAS  Google Scholar 

  • Frame MC, Patel H, Serrels B et al (2010) The FERM domain: organizing the structure and function of FAK. Nat Rev Mol Cell Biol 11:802–814

    Article  PubMed  CAS  Google Scholar 

  • Garces CA et al (2006) Vascular endothelial growth factor receptor-3 and focal adhesion kinase bind and suppress apoptosis in breast cancer cells. Cancer Res 66:1446–1454

    Article  PubMed  CAS  Google Scholar 

  • Golubovskaya VM, Conway-Dorsey K, Edmiston SN et al (2009a) FAK overexpression and p53 mutations are highly correlated in human breast cancer. Int J Cancer 125:1735–1738

    Article  PubMed  CAS  Google Scholar 

  • Golubovskaya VM, Kweh FA, Cance WG (2009b) Focal adhesion kinase and cancer. Histol Histopathol 24:503–510

    PubMed  CAS  Google Scholar 

  • Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674

    Article  PubMed  CAS  Google Scholar 

  • Hirsch FR, Spreafico A, Novello S et al (2008) The prognostic and predictive role of histology in advanced non-small cell lung cancer: a literature review. J Thorac Oncol 3:1468–1481

    Article  PubMed  Google Scholar 

  • Jemal A, Siegel R, Xu J et al (2010) Cancer statistics 2010. CA Cancer J Clin 60:277–300

    Article  PubMed  Google Scholar 

  • Kurio N, Shimo T, Fukazawa T et al (2011) Anti-tumor effect in human breast cancer by TAE226, a dual inhibitor for FAK and IGF-IR in vitro and in vivo. Exp Cell Res 317:1134–1146

    Article  PubMed  CAS  Google Scholar 

  • Lesslie DP, Summy JM, Parikh NU et al (2006) Vascular endothelial growth factor receptor-1 mediates migration of human colorectal carcinoma cells by activation of Src family kinases. Br J Cancer 94:1710–1717

    PubMed  CAS  Google Scholar 

  • Ma WW (2011) Development of focal adhesion kinase inhibitors in cancer therapy. Anticancer Agents Med Chem 11:638–642

    Article  PubMed  CAS  Google Scholar 

  • McLean GW, Carragher NO, Avizienyte E et al (2005) The role of focal-adhesion kinase in cancer-a new therapeutic opportunity. Nat Rev Cancer 5:505–515

    Article  PubMed  CAS  Google Scholar 

  • Mehlen P, Puisieux A (2006) Metastasis: a question of life or death. Nat Rev Cancer 6:449–458

    Article  PubMed  CAS  Google Scholar 

  • Meng XN, Jin Y, Yu Y et al (2009) Characterisation of fibronectin-mediated FAK signalling pathways in lung cancer cell migration and invasion. Br J Cancer 101:327–334

    Article  PubMed  CAS  Google Scholar 

  • Mitra SK, Hanson DA, Schlaepfer DD (2005) Focal adhesion kinase: in command and control of cell motility. Nat Rev Mol Cell Biol 6:56–68

    Article  PubMed  CAS  Google Scholar 

  • Ocak S, Yamashita H, Udyavar AR et al (2010) DNA copy number aberrations in small-cell lung cancer reveal activation of the focal adhesion pathway. Oncogene 29:6331–6342

    Article  PubMed  CAS  Google Scholar 

  • Ocak S, Chen H, Callison C et al (2012) Expression of focal adhesion kinase in small-cell lung carcinoma. Cancer 118:1293–1301

    Article  PubMed  CAS  Google Scholar 

  • Paez JG, Janne PA, Lee JC et al (2004) EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 304:1497–1500

    Article  PubMed  CAS  Google Scholar 

  • Provenzano PP, Keely PJ (2009) The role of focal adhesion kinase in tumor initiation and progression. Cell Adh Migr 3:347–350

    Article  PubMed  Google Scholar 

  • Roberts WG, Ung E, Whalen P et al (2008) Antitumor activity and pharmacology of a selective focal adhesion kinase inhibitor, PF-562,271. Cancer Res 68:1935–1944

    Article  PubMed  CAS  Google Scholar 

  • Sandler A, Gray R, Perry MC et al (2006) Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 355:2542–2550

    Article  PubMed  CAS  Google Scholar 

  • Schwock J, Dhani N, Hedley DW (2010) Targeting focal adhesion kinase signaling in tumor growth and metastasis. Expert Opin Ther Targets 14:77–94

    Article  PubMed  CAS  Google Scholar 

  • Shibue T, Weinberg RA (2009) Integrin beta1-focal adhesion kinase signalin2010 g directs the proliferation of metastatic cancer cells disseminated in the lungs. Proc Natl Acad Sci USA 106:10290–10295

    Article  PubMed  CAS  Google Scholar 

  • Sieg DJ, Hauck CR, Ilic D et al (2000) FAKintegrates growth-factor and integrin signals to promote cell migration. Nat Cell Biol 2:249–256

    Article  PubMed  CAS  Google Scholar 

  • Slack-Davis JK, Martin KH, Tilghman RW et al (2007) Cellular characterization of a novel focal adhesion kinase inhibitor. J Biol Chem 282:14845–14852

    Article  PubMed  CAS  Google Scholar 

  • Steeg PS, Theodorescu D (2008) Metastasis: a therapeutic target for cancer. Nat Clin Pract Oncol 5:206–219

    Article  PubMed  CAS  Google Scholar 

  • Tomar A, Schlaepfer DD (2010) A PAK-activated linker for EGFR and FAK. Dev Cell 18:170–172

    Article  PubMed  CAS  Google Scholar 

  • Walsh C, Tanjoni I, Uryu S et al (2010) Oral delivery of PND-1186 FAK inhibitor decreases tumor growth and spontaneous breast to lung metastasis in pre-clinical models. Cancer Biol Ther 9:778–790

    Article  PubMed  CAS  Google Scholar 

  • Webb DJ, Donais K, Whitmore LA et al (2004) FAK-Src signalling through paxillin, ERK and MLCK regulates adhesion disassembly. Nat Cell Biol 6:154–161

    Article  PubMed  CAS  Google Scholar 

  • Zheng D, Golubovskaya V, Kurenova E et al (2010) A novel strategy to inhibit FAK and IGF-1R decreases growth of pancreatic cancer xenografts. Mol Carcinog 49:200–209

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors thank Qi HUANG, Department of Pathology of Harbin Medical University, for her excellent technical assistance with the immunohistochemical studies, and also thank all patients for providing tissue samples. This study was supported by a grant from Provincial Research Projects of Heilongjiang (No. GB08C401-01).

Conflict of interest

The authors declare no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Da Pang or Song-Bin Fu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ji, HF., Pang, D., Fu, SB. et al. Overexpression of focal adhesion kinase correlates with increased lymph node metastasis and poor prognosis in non-small-cell lung cancer. J Cancer Res Clin Oncol 139, 429–435 (2013). https://doi.org/10.1007/s00432-012-1342-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00432-012-1342-8

Keywords

Navigation