Radiotherapy & Oncology
Volume 92, Issue 3 , Pages 371-378 , September 2009

3D cell cultures of human head and neck squamous cell carcinoma cells are radiosensitized by the focal adhesion kinase inhibitor TAE226

  • Stephanie Hehlgans
  • ,
  • Inga Lange
  • ,
  • Iris Eke
  • ,
  • Nils Cordes

      Affiliations

    • Corresponding Author InformationCorresponding author. Address: OncoRay – Center for Radiation Research in Oncology, Medical Faculty Carl Gustav Carus, Dresden University of Technology, Fetscherstrasse 74, 01307 Dresden, Germany.

Received 27 April 2009 ,Revised 1 July 2009 ,Accepted 7 August 2009.

References 

  1. Baumann M, Krause M, Hill R. Exploring the role of cancer stem cells in radioresistance. Nat Rev Cancer. 2008;8:545–554
  2. Dean M. Cancer stem cells: redefining the paradigm of cancer treatment strategies. Mol Interv. 2006;6:140–148
  3. Dean M, Fojo T, Bates S. Tumour stem cells and drug resistance. Nat Rev Cancer. 2005;5:275–284
  4. Milas L, Raju U, Liao Z, Ajani J. Targeting molecular determinants of tumor chemo-radioresistance. Semin Oncol. 2005;32:S78–S81
  5. Baumann M, Krause M, Dikomey E, et al. EGFR-targeted anti-cancer drugs in radiotherapy: preclinical evaluation of mechanisms. Radiother Oncol. 2007;83:238–248
  6. Cordes N, Meineke V. Cell adhesion-mediated radioresistance (CAM-RR) extracellular matrix-dependent improvement of cell survival in human tumor and normal cells in vitro. Strahlenther Onkol. 2003;179:337–344
  7. Hehlgans S, Haase M, Cordes N. Signalling via integrins: implications for cell survival and anticancer strategies. Biochim Biophys Acta. 2007;1775:163–180
  8. Jacobs CI. A review of the role of insulin-like growth factor 2 in malignancy and its potential as a modifier of radiation sensitivity. Clin Oncol [R Coll Radiol]. 2008;20:345–352
  9. Eke I, Sandfort V, Mischkus A, Baumann M, Cordes N. Antiproliferative effects of EGFR tyrosine kinase inhibition and radiation-induced genotoxic injury are attenuated by adhesion to fibronectin. Radiother Oncol. 2006;80:178–184
  10. Eke I, Sandfort V, Storch K, Baumann M, Roper B, Cordes N. Pharmacological inhibition of EGFR tyrosine kinase affects ILK-mediated cellular radiosensitization in vitro. Int J Radiat Biol. 2007;83:793–802
  11. Parsons JT, Slack-Davis J, Tilghman R, Roberts WG. Focal adhesion kinase: targeting adhesion signaling pathways for therapeutic intervention. Clin Cancer Res. 2008;14:627–632
  12. Sastry SK, Burridge K. Focal adhesions: a nexus for intracellular signaling and cytoskeletal dynamics. Exp Cell Res. 2000;261:25–36
  13. Cance WG, Harris JE, Iacocca MV, et al. 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. 2000;6:2417–2423
  14. Glukhova M, Koteliansky V, Sastre X, Thiery JP. Adhesion systems in normal breast and in invasive breast carcinoma. Am J Pathol. 1995;146:706–716
  15. Han NM, Fleming RY, Curley SA, Gallick GE. Overexpression of focal adhesion kinase (p125FAK) in human colorectal carcinoma liver metastases: independence from c-src or c-yes activation. Ann Surg Oncol. 1997;4:264–268
  16. Hsu NY, Chen CY, Hsu CP, et al. Prognostic significance of expression of nm23–H1 and focal adhesion kinase in non-small cell lung cancer. Oncol Rep. 2007;18:81–85
  17. Kornberg LJ. Focal adhesion kinase expression in oral cancers. Head Neck. 1998;20:634–639
  18. Owens LV, Xu L, Craven RJ, et al. Overexpression of the focal adhesion kinase (p125FAK) in invasive human tumors. Cancer Res. 1995;55:2752–2755
  19. Sakurama K, Noma K, Takaoka M, et al. Inhibition of focal adhesion kinase as a potential therapeutic strategy for imatinib-resistant gastrointestinal stromal tumor. Mol Cancer Ther. 2009;8:127–134
  20. Sood AK, Coffin JE, Schneider GB, et al. Biological significance of focal adhesion kinase in ovarian cancer: role in migration and invasion. Am J Pathol. 2004;165:1087–1095
  21. Beinke C, Van Beuningen D, Cordes N. Ionizing radiation modules of the expression and tyrosine phosphorylation of the focal adhesion-associated proteins focal adhesion kinase (FAK) and its substrates p130cas and paxillin in A549 human lung carcinoma cells in vitro. Int J Radiat Biol. 2003;79:721–731
  22. Cordes N, Frick S, Brunner TB, et al. Human pancreatic tumor cells are sensitized to ionizing radiation by knockdown of caveolin-1. Oncogene. 2007;26:6851–6862
  23. Kasahara T, Koguchi E, Funakoshi M, Aizu-Yokota E, Sonoda Y. Antiapoptotic action of focal adhesion kinase (FAK) against ionizing radiation. Antioxid Redox Signal. 2002;4:491–499
  24. McLean GW, Carragher NO, Avizienyte E, Evans J, Brunton VG, Frame MC. The role of focal-adhesion kinase in cancer – a new therapeutic opportunity. Nat Rev Cancer. 2005;5:505–515
  25. Sonoda Y, Matsumoto Y, Funakoshi M, Yamamoto D, Hanks SK, Kasahara T. Anti-apoptotic role of focal adhesion kinase (FAK). Induction of inhibitor-of-apoptosis proteins and apoptosis suppression by the overexpression of FAK in a human leukemic cell line, HL-60. J Biol Chem. 2000;275:16309–16315
  26. Yee KL, Weaver VM, Hammer DA. Integrin-mediated signalling through the MAP-kinase pathway. IET Syst Biol. 2008;2:8–15
  27. Lim ST, Mikolon D, Stupack DG, Schlaepfer DD. FERM control of FAK function: implications for cancer therapy. Cell Cycle. 2008;7:2306–2314
  28. Zhao J, Guan JL. Signal transduction by focal adhesion kinase in cancer. Cancer Metastasis Rev. 2009;
  29. Beierle EA, Trujillo A, Nagaram A, et al. N-MYC regulates focal adhesion kinase expression in human neuroblastoma. J Biol Chem. 2007;282:12503–12516
  30. Golubovskaya V, Beviglia L, Xu LH, Earp HS, Craven R, Cance W. Dual inhibition of focal adhesion kinase and epidermal growth factor receptor pathways cooperatively induces death receptor-mediated apoptosis in human breast cancer cells. J Biol Chem. 2002;277:38978–38987
  31. Halder J, Landen CN, Lutgendorf SK, et al. Focal adhesion kinase silencing augments docetaxel-mediated apoptosis in ovarian cancer cells. Clin Cancer Res. 2005;11:8829–8836
  32. Xu LH, Yang X, Bradham CA, et al. The focal adhesion kinase suppresses transformation-associated, anchorage-independent apoptosis in human breast cancer cells. Involvement of death receptor-related signaling pathways. J Biol Chem. 2000;275:30597–30604
  33. Roberts WG, Ung E, Whalen P, et al. Antitumor activity and pharmacology of a selective focal adhesion kinase inhibitor, PF-562, 271. Cancer Res. 2008;68:1935–1944
  34. Slack-Davis JK, Martin KH, Tilghman RW, et al. Cellular characterization of a novel focal adhesion kinase inhibitor. J Biol Chem. 2007;282:14845–14852
  35. Beierle EA, Trujillo A, Nagaram A, Golubovskaya VM, Cance WG, Kurenova EV. TAE226 inhibits human neuroblastoma cell survival. Cancer Invest. 2008;26:145–151
  36. Golubovskaya VM, Virnig C, Cance WG. TAE226-induced apoptosis in breast cancer cells with overexpressed Src or EGFR. Mol Carcinog. 2008;47:222–234
  37. Shi Q, Hjelmeland AB, Keir ST, et al. A novel low-molecular weight inhibitor of focal adhesion kinase, TAE226, inhibits glioma growth. Mol Carcinog. 2007;46:488–496
  38. Wang ZG, Fukazawa T, Nishikawa T, et al. TAE226, a dual inhibitor for FAK and IGF-IR, has inhibitory effects on mTOR signaling in esophageal cancer cells. Oncol Rep. 2008;20:1473–1477
  39. Watanabe N, Takaoka M, Sakurama K, et al. Dual tyrosine kinase inhibitor for focal adhesion kinase and insulin-like growth factor-I receptor exhibits anticancer effect in esophageal adenocarcinoma in vitro and in vivo. Clin Cancer Res. 2008;14:4631–4639
  40. Hehlgans S, Eke I, Deuse Y, Cordes N. Integrin-linked kinase: dispensable for radiation survival of three-dimensionally cultured fibroblasts. Radiother Oncol. 2008;86:329–335
  41. Yaromina A, Krause M, Thames H, et al. Pre-treatment number of clonogenic cells and their radiosensitivity are major determinants of local tumour control after fractionated irradiation. Radiother Oncol. 2007;83:304–310
  42. Sawada M, Sato M. The effect of dimethyl sulfoxide on the neuronal excitability and cholinergic transmission in aplysia ganglion cells. Ann NY Acad Sci. 1975;243:337–357
  43. Fukumoto H, Matsui Y, Obinata M. Mechanism of erythropoietin action on the erythroid progenitor cells induced from murine erythroleukemia cells (TSA8). Development. 1989;105:109–114
  44. Absolom DR, Neumann AW, Zingg W, van Oss CJ. Thermodynamic studies of cellular adhesion. Trans Am Soc Artif Intern Organs. 1979;25:152–158
  45. McIntyre LJ, Kim YS. Effects of sodium butyrate and dimethylsulfoxide on human pancreatic tumor cell lines. Eur J Cancer Clin Oncol. 1984;20:265–271
  46. Janes SM, Watt FM. New roles for integrins in squamous-cell carcinoma. Nat Rev Cancer. 2006;6:175–183
  47. al-Obeidi FA, Wu JJ, Lam KS. Protein tyrosine kinases: structure, substrate specificity, and drug discovery. Biopolymers. 1998;47:197–223
  48. Ross GM. Induction of cell death by radiotherapy. Endocr Relat Cancer. 1999;6:41–44

PII: S0167-8140(09)00434-4

doi: 10.1016/j.radonc.2009.08.001

Radiotherapy & Oncology
Volume 92, Issue 3 , Pages 371-378 , September 2009