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Focal adhesion kinase serves as a marker of cervical lymph node metastasis and is a potential therapeutic target in tongue cancer

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Abstract

Purpose

The aims of the present study were to examine whether focal adhesion kinase (FAK) expression is correlated with cervical lymph node metastasis of tongue cancer and to investigate the roles of FAK in the process of cancer cell migration, invasion and anoikis resistance using the human tongue cancer cell line, Tca8113.

Methods

FAK expression was evaluated in 5 normal oral mucosa, 10 premalignant lesions, 80 primary tongue cancers and 41 lymph node metastases using anti-FAK immunohistochemistry. The migration, invasion and anoikis resistance of tongue cancer cells were evaluated using wound healing assays, invasion assays and anoikis induction. The effect of FAK inhibition was evaluated using RNA interference (RNAi).

Results

In total, 55 of 80 primary tongue cancers (69%) showed high expression of FAK, and 25 of 80 tumors (31%) and all normal oral mucosa or premalignant lesions showed low expression of FAK. There was a significant correlation between FAK expression and the cervical lymph node metastasis of tongue cancer. Moreover, RNAi-mediated FAK reduction decreased tongue cancer cell migration, invasion and anoikis resistance.

Conclusions

These results suggest that FAK may serve as a marker of cervical lymph node metastasis of tongue cancer and that RNAi targeting FAK could serve as a potential therapeutic for the treatment of tongue cancer.

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References

  • Ayaki M, Komatsu K, Mukai M, Murata K, Kameyama M, Ishiguro S et al (2001) Reduced expression of focal adhesion kinase in liver metastases compared with matched primary human colorectal adenocarcinomas. Clin Cancer Res 7:3106–3112

    CAS  PubMed  Google Scholar 

  • Bànkfalvi A, Piffkò J (2000) Prognostic and predictive factors in oral cancer: the role of the invasive tumour front. J Oral Pathol Med 29:291–298

    Article  PubMed  Google Scholar 

  • Bettendorfa O, Plffko J, Bànkfalvi A (2004) Prognostic and predictive factors in oral squamous cell cancer: important tools for planning individual therapy? Oral Oncol 40:110–119

    Article  Google Scholar 

  • Cance WG, Harris JE, Iacocca MV, Roche E, Yang XH, Chang J et al (2000) Immunohistochemical analyses of focal adhesion kinase expression in benign and malignant human breast and colon tissues: correlation with preinvasive and invasive phenotypes. Clin Cancer Res 6:2417–2423

    CAS  PubMed  Google Scholar 

  • Canel M, Secades P, Rodrigo JP, Cabanillas R, Herrero A, Suarez C et al (2006) Overexpression of focal adhesion kinase in head and neck squamous cell carcinoma is independent of fak gene copy number. Clin Cancer Res 12:3272–3279

    Article  CAS  PubMed  Google Scholar 

  • Cicchini C, Laudadio I, Citarella F, Corazzari M, Steindler C, Conigliaro A et al (2008) TGFβ-induced EMT requires focal adhesion kinase (FAK) signaling. Exp Cell Res 314:143–152

    Article  CAS  PubMed  Google Scholar 

  • Díaz-Montero CM, Wygant JN, McIntyre BW (2006) PI3-K/Akt-mediated anoikis resistance of human osteosarcoma cells requires Src activation. Eur J Cancer 42:1491–1500

    Article  PubMed  Google Scholar 

  • Duxbury MS, Ito H, Zinner MJ, Ashley SW, Whang EE (2004) Focal adhesion kinase gene silencing promotes anoikis and suppresses metastasis of human pancreatic adenocarcinoma cells. Surgery 135:555–562

    Article  CAS  PubMed  Google Scholar 

  • Folkman J, Moscona A (1978) Role of cell shape in growth control. Nature 273:345–349

    Article  CAS  PubMed  Google Scholar 

  • Forastiere A, Koch W, Trotti A, Sidransky D (2001) Head and neck cancer. N Engl J Med 345:1890–1900

    Article  CAS  PubMed  Google Scholar 

  • Frisch SM, Screaton RA (2001) Anoikis mechanisms. Curr Opin Cell Biol 13:555–562

    Article  CAS  PubMed  Google Scholar 

  • Furuyama K, Doi R, Mori T, Toyoda E, Ito D, Kami K et al (2006) Clinical significance of focal adhesion kinase in respectable pancreatic cancer. World J Surg 30:219–226

    Article  PubMed  Google Scholar 

  • Gabriel B, Zur HA, Stickeler E, Dietz C, Gitsch G, Fischer DC et al (2006) Weak expression of focal adhesion kinase (pp125FAK) in patients with cervical cancer is associated with poor disease outcome. Clin Cancer Res 12:2476–2483

    Article  CAS  PubMed  Google Scholar 

  • Keski-Santti H, Atula T, Tikka J, Hollmen J, Makitie AA, Leivo I (2007) Predictive value of histopathologic parameters in early squamous cell carcinoma of oral tongue. Oral Oncol 43:1007–1013

    Article  PubMed  Google Scholar 

  • Kupferman ME, Patel V, Sriuranpong V, Amornphimoltham P, Jasser SA, Mandal M et al (2007) Molecular analysis of anoikis resistance in oral cavity squamous cell carcinoma. Oral Oncol 43:440–454

    Article  CAS  PubMed  Google Scholar 

  • Lark AL, Livasy CA, Calvo B, Caskey L, Moore DT, Yang XH et al (2003) Overexpression of focal adhesion kinase in primary colorectal carcinomas and colorectal liver metastases: immunohistochemistry and real-time PCR analyses. Clin Cancer Res 9:215–222

    CAS  PubMed  Google Scholar 

  • Lim SC, Zhang S, Ishii G, Endoh Y, Kodama K, Miyamoto S et al (2004) Predictive markers for late cervical metastasis in stage I and II invasive squamous cell carcinoma of the oral tongue. Clin Cancer Res 10:166–172

    Article  CAS  PubMed  Google Scholar 

  • Mishima K, Inoue K, Hayashi Y (2002) Overexpression of extracellular-signal regulated kinases on oral squamous cell carcinoma. Oral Oncol 38:468–474

    Article  CAS  PubMed  Google Scholar 

  • Miyazaki T, Kato H, Nakajima M, Sohda M, Fukai Y, Masuda N et al (2003) FAK overexpression is correlated with tumour invasiveness and lymph node metastasis in oesophageal squamous cell carcinoma. Br J Cancer 89:140–145

    Article  CAS  PubMed  Google Scholar 

  • Noguchi M, Kinjyo H, Kohama G, Nakamori K (2002) Invasive front in oral squamous cell carcinoma: image and flow cytometric analysis with clinicopathologic correlation. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 93:682–687

    Article  PubMed  Google Scholar 

  • Rodrigo JP, Dominguez F, Suárez V, Canel M, Secades P, Chiara MD (2007) Focal adhesion kinase and E-cadherin as markers for nodal metastasis in laryngeal cancer. Arch Otolaryngol Head Neck Surg 133:145–150

    Article  PubMed  Google Scholar 

  • Sankaranarayanan R, Masuer E, Swaminathan R, Ferlay J, Whelan S (1998) Head and neck cancer: a global perspective on epidemiology and prognosis. Anticancer Res 18:4779–4786

    CAS  PubMed  Google Scholar 

  • Schaller MD, Borgmana CA, Cobb BS, Vines RR, Reynolds AB, Parsons JT (1992) pp125FAK, a structurally unique protein tyrosine kinase associated with focal adhesions. Proc Natl Acad Sci USA 89:5192–5196

    Article  CAS  PubMed  Google Scholar 

  • Scheneider GB, Kurago Z, Zaharias R, Gruman LM, Schaller MD, Hendrix MJ (2002) Elevated focal adhesion kinase expression facilitates oral tumor cell invasion. Cancer 95:2508–2515

    Article  Google Scholar 

  • Schlaepfer DD, Mitra SK (2004) Multiple connections link FAK to cell motility and invasion. Curr Opin Genet Dev 14:92–101

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Siesser MF, Hanks SK (2006) The signaling and biological implications of FAK overexpression in cancer. Clin Cancer Res 12:3233–3236

    Article  CAS  PubMed  Google Scholar 

  • Sonoda Y, Matsumoto Y, Funakoshi M, Yamamoto D, Hanks SK, Kasahara T (2000) Anti-apoptotic role of focal adhesion kinase (FAK). J Biol Chem 275:16309–16315

    Article  CAS  PubMed  Google Scholar 

  • Swan EA, Jasser SA, Holsinger FC, Doan D, Bucana C, Myers JN (2003) Acquisition of anoikis resistance is a critical step in the progression of oral tongue cancer. Oral Oncol 39:648–655

    Article  CAS  PubMed  Google Scholar 

  • Theocharis SE, Kouraklis GP, Kakisis JD, Kanelli HG, Apostolakou FE, Karatzas GM et al (2002) Focal adhesion kinase expression is not a prognostic predictor in colon adenocarcinoma patients. Eur J Surg Oncol 29:571–574

    Article  Google Scholar 

  • van Nimwegen MJ, van de Water B (2007) Focal adhesion kinase: a potential target in cancer therapy. Biochem Pharmacol 73:597–609

    Article  CAS  PubMed  Google Scholar 

  • Watermann DO, Gabriel B, Jager M, Orlowska-Volk M, Hasenburg A, Zur HA et al (2005) Specific induction of pp125 focal adhesion kinase in human breast cancer. Br J Cancer 93:694–698

    Article  CAS  PubMed  Google Scholar 

  • Zhang Y, Lu H, Dazin P, Kapila Y (2004) Squamous cell carcinoma cell aggregates escape suspension-induced, p53-mediated anoikis: fibronectin and integrin alphav mediate survival signals through focal adhesion kinase. J Biol Chem 279:48342–48349

    Article  CAS  PubMed  Google Scholar 

  • Ziober BL, Silverman SS, Kramer RH (2001) Adhesive mechanisms regulating invasion and metastasis in oral cancer. Crit Rev Oral Biol Med 12:499–510

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by the Grants H200636 and H200753 from the Health Bureau of Jiangsu province and the Science and Technology Development Foundation of Nanjing Medical University (2005NYDZD25).

Conflict of interest statement

We have no potential conflicts of interest.

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Authors and Affiliations

  1. Department of Oral and Maxillofacial Surgery, School of Stomatology, Nanjing Medical University, Nanjing, 210029, Jiangsu, People’s Republic of China

    Hongbing Jiang, Jinhai Ye, Hualian Liu, Shuzhong Xing & Yunong Wu

  2. Department of Oral Pathology, School of Stomatology, Nanjing Medical University, Nanjing, 210029, Jiangsu, People’s Republic of China

    Laikui Liu

  3. Institute of Stomatology, School of Stomatology, Nanjing Medical University, Nanjing, 210029, Jiangsu, People’s Republic of China

    Hongbing Jiang, Laikui Liu & Jinhai Ye

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  1. Hongbing Jiang
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  2. Laikui Liu
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  4. Hualian Liu
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Correspondence to Hongbing Jiang.

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Jiang, H., Liu, L., Ye, J. et al. Focal adhesion kinase serves as a marker of cervical lymph node metastasis and is a potential therapeutic target in tongue cancer. J Cancer Res Clin Oncol 136, 1295–1302 (2010). https://doi.org/10.1007/s00432-010-0780-4

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  • DOI: https://doi.org/10.1007/s00432-010-0780-4

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