Skip to main content
Top
Published in: Journal of Cancer Research and Clinical Oncology 9/2010

01-09-2010 | Original Paper

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

Authors: Hongbing Jiang, Laikui Liu, Jinhai Ye, Hualian Liu, Shuzhong Xing, Yunong Wu

Published in: Journal of Cancer Research and Clinical Oncology | Issue 9/2010

Login to get access

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.
Literature
go back to reference 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 7:3106–3112PubMed 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 7:3106–3112PubMed
go back to reference Bànkfalvi A, Piffkò J (2000) Prognostic and predictive factors in oral cancer: the role of the invasive tumour front. J Oral Pathol Med 29:291–298CrossRefPubMed Bànkfalvi A, Piffkò J (2000) Prognostic and predictive factors in oral cancer: the role of the invasive tumour front. J Oral Pathol Med 29:291–298CrossRefPubMed
go back to reference Bettendorfa O, Plffko J, Bànkfalvi A (2004) Prognostic and predictive factors in oral squamous cell cancer: important tools for planning individual therapy? Oral Oncol 40:110–119CrossRef Bettendorfa O, Plffko J, Bànkfalvi A (2004) Prognostic and predictive factors in oral squamous cell cancer: important tools for planning individual therapy? Oral Oncol 40:110–119CrossRef
go back to reference 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 6:2417–2423PubMed 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 6:2417–2423PubMed
go back to reference 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 12:3272–3279CrossRefPubMed 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 12:3272–3279CrossRefPubMed
go back to reference 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 314:143–152CrossRefPubMed 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 314:143–152CrossRefPubMed
go back to reference Díaz-Montero CM, Wygant JN, McIntyre BW (2006) PI3-K/Akt-mediated anoikis resistance of human osteosarcoma cells requires Src activation. Eur J Cancer 42:1491–1500CrossRefPubMed Díaz-Montero CM, Wygant JN, McIntyre BW (2006) PI3-K/Akt-mediated anoikis resistance of human osteosarcoma cells requires Src activation. Eur J Cancer 42:1491–1500CrossRefPubMed
go back to reference 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 135:555–562CrossRefPubMed 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 135:555–562CrossRefPubMed
go back to reference Forastiere A, Koch W, Trotti A, Sidransky D (2001) Head and neck cancer. N Engl J Med 345:1890–1900CrossRefPubMed Forastiere A, Koch W, Trotti A, Sidransky D (2001) Head and neck cancer. N Engl J Med 345:1890–1900CrossRefPubMed
go back to reference 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 30:219–226CrossRefPubMed 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 30:219–226CrossRefPubMed
go back to reference 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 12:2476–2483CrossRefPubMed 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 12:2476–2483CrossRefPubMed
go back to reference 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 43:1007–1013CrossRefPubMed 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 43:1007–1013CrossRefPubMed
go back to reference 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 43:440–454CrossRefPubMed 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 43:440–454CrossRefPubMed
go back to reference 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 9:215–222PubMed 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 9:215–222PubMed
go back to reference 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 10:166–172CrossRefPubMed 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 10:166–172CrossRefPubMed
go back to reference Mishima K, Inoue K, Hayashi Y (2002) Overexpression of extracellular-signal regulated kinases on oral squamous cell carcinoma. Oral Oncol 38:468–474CrossRefPubMed Mishima K, Inoue K, Hayashi Y (2002) Overexpression of extracellular-signal regulated kinases on oral squamous cell carcinoma. Oral Oncol 38:468–474CrossRefPubMed
go back to reference 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 89:140–145CrossRefPubMed 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 89:140–145CrossRefPubMed
go back to reference 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 93:682–687CrossRefPubMed 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 93:682–687CrossRefPubMed
go back to reference 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 133:145–150CrossRefPubMed 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 133:145–150CrossRefPubMed
go back to reference Sankaranarayanan R, Masuer E, Swaminathan R, Ferlay J, Whelan S (1998) Head and neck cancer: a global perspective on epidemiology and prognosis. Anticancer Res 18:4779–4786PubMed Sankaranarayanan R, Masuer E, Swaminathan R, Ferlay J, Whelan S (1998) Head and neck cancer: a global perspective on epidemiology and prognosis. Anticancer Res 18:4779–4786PubMed
go back to reference 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 89:5192–5196CrossRefPubMed 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 89:5192–5196CrossRefPubMed
go back to reference Scheneider GB, Kurago Z, Zaharias R, Gruman LM, Schaller MD, Hendrix MJ (2002) Elevated focal adhesion kinase expression facilitates oral tumor cell invasion. Cancer 95:2508–2515CrossRef Scheneider GB, Kurago Z, Zaharias R, Gruman LM, Schaller MD, Hendrix MJ (2002) Elevated focal adhesion kinase expression facilitates oral tumor cell invasion. Cancer 95:2508–2515CrossRef
go back to reference Schlaepfer DD, Mitra SK (2004) Multiple connections link FAK to cell motility and invasion. Curr Opin Genet Dev 14:92–101CrossRefPubMed Schlaepfer DD, Mitra SK (2004) Multiple connections link FAK to cell motility and invasion. Curr Opin Genet Dev 14:92–101CrossRefPubMed
go back to reference Sieg DJ, Hauck CR, Ilic D et al (2000) FAK integrates growth factor and integrin signals to promote cell migration. Nat Cell Biol 2:249–256CrossRefPubMed Sieg DJ, Hauck CR, Ilic D et al (2000) FAK integrates growth factor and integrin signals to promote cell migration. Nat Cell Biol 2:249–256CrossRefPubMed
go back to reference Siesser MF, Hanks SK (2006) The signaling and biological implications of FAK overexpression in cancer. Clin Cancer Res 12:3233–3236CrossRefPubMed Siesser MF, Hanks SK (2006) The signaling and biological implications of FAK overexpression in cancer. Clin Cancer Res 12:3233–3236CrossRefPubMed
go back to reference Sonoda Y, Matsumoto Y, Funakoshi M, Yamamoto D, Hanks SK, Kasahara T (2000) Anti-apoptotic role of focal adhesion kinase (FAK). J Biol Chem 275:16309–16315CrossRefPubMed Sonoda Y, Matsumoto Y, Funakoshi M, Yamamoto D, Hanks SK, Kasahara T (2000) Anti-apoptotic role of focal adhesion kinase (FAK). J Biol Chem 275:16309–16315CrossRefPubMed
go back to reference 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 39:648–655CrossRefPubMed 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 39:648–655CrossRefPubMed
go back to reference 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 29:571–574CrossRef 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 29:571–574CrossRef
go back to reference van Nimwegen MJ, van de Water B (2007) Focal adhesion kinase: a potential target in cancer therapy. Biochem Pharmacol 73:597–609CrossRefPubMed van Nimwegen MJ, van de Water B (2007) Focal adhesion kinase: a potential target in cancer therapy. Biochem Pharmacol 73:597–609CrossRefPubMed
go back to reference 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 93:694–698CrossRefPubMed 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 93:694–698CrossRefPubMed
go back to reference 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 279:48342–48349CrossRefPubMed 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 279:48342–48349CrossRefPubMed
go back to reference Ziober BL, Silverman SS, Kramer RH (2001) Adhesive mechanisms regulating invasion and metastasis in oral cancer. Crit Rev Oral Biol Med 12:499–510CrossRefPubMed Ziober BL, Silverman SS, Kramer RH (2001) Adhesive mechanisms regulating invasion and metastasis in oral cancer. Crit Rev Oral Biol Med 12:499–510CrossRefPubMed
Metadata
Title
Focal adhesion kinase serves as a marker of cervical lymph node metastasis and is a potential therapeutic target in tongue cancer
Authors
Hongbing Jiang
Laikui Liu
Jinhai Ye
Hualian Liu
Shuzhong Xing
Yunong Wu
Publication date
01-09-2010
Publisher
Springer-Verlag
Published in
Journal of Cancer Research and Clinical Oncology / Issue 9/2010
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-010-0780-4

Other articles of this Issue 9/2010

Journal of Cancer Research and Clinical Oncology 9/2010 Go to the issue