nach oben

Journal of Cancer Research and Clinical Oncology

Erschienen in:

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

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

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 9/2010

Einloggen, um Zugang zu erhalten

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.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Titel: Focal adhesion kinase serves as a marker of cervical lymph node metastasis and is a potential therapeutic target in tongue cancer
verfasst von: Hongbing Jiang
Laikui Liu
Jinhai Ye
Hualian Liu
Shuzhong Xing
Yunong Wu
Publikationsdatum: 01.09.2010
Verlag: Springer-Verlag
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 9/2010
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-010-0780-4

Springer Medizin

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

Abstract

Purpose

Methods

Results

Conclusions

Neu im Fachgebiet Onkologie

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Update Onkologie

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusions

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 9/2010

Effect of misdiagnosis on the prognosis of anorectal malignant melanoma

Benefit of radiotherapy for 90 patients with resected intrahepatic cholangiocarcinoma and concurrent lymph node metastases

Altered expression of p120catenin predicts poor outcome in invasive breast cancer

Epigenetic alterations in disseminated neuroblastoma tumour cells: influence of TMS1 gene hypermethylation in relapse risk in NB patients

PTEN mutation spectrum in breast cancers and breast hyperplasia

Peripheral blood gene expression of B7 and CD28 family members associated with tumor progression and microscopic lymphovascular invasion in colon cancer patients

Neu im Fachgebiet Onkologie

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Update Onkologie