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Pharmacological inhibition of EGFR tyrosine kinase affects ILK-mediated cellular radiosensitization in vitro

Iris Eke1, Veit Sandfort, Katja Storch

  • 1OncoRay - Center for Radiation Research in Oncology, Medical Faculty Carl Gustav Carus, Dresden University of Technology, Dresden, Germany.

International Journal of Radiation Biology
|December 7, 2007
PubMed
Abstract

Insights

Integrin-linked kinase (ILK) enhances radiosensitization by reducing DNA repair, but this effect depends on epidermal growth factor receptor (EGFR) tyrosine kinase activity. Inhibiting EGFR-tk diminishes ILK-mediated radiosensitization.

Area of Science:

  • Cell biology
  • Molecular oncology
  • Radiation oncology

Background:

  • Integrin-linked kinase (ILK) is a key signaling molecule linking beta integrins to the epidermal growth factor receptor (EGFR).
  • ILK has demonstrated an antisurvival effect in irradiated cells, suggesting a role in radiosensitization.

Purpose of the Study:

  • To investigate the role of EGFR tyrosine kinase (tk) activity in ILK-mediated radiosensitization.
  • To determine if EGFR-tk inhibition affects the radiosensitizing properties of ILK.

Main Methods:

  • Utilized human FaDu squamous cell carcinoma cells with hyperactive ILK (ILK-hk) and ILK knockout (ILK(-/-)) mouse fibroblasts.
  • Treated cells with the EGFR-tk inhibitor BIBX1382BS, with or without X-ray irradiation.
  • Assessed clonogenic survival, protein expression/phosphorylation (EGFR, Akt, MAPK), DNA double-strand break (DSB) repair, cell morphology, and cell cycle distribution.

Main Results:

  • ILK-hk and ILK(fl/fl) expression significantly radiosensitized cells compared to controls.
  • EGFR-tk inhibition with BIBX1382BS diminished ILK-hk-mediated radiosensitization without affecting normal fibroblast survival.
  • ILK-hk-mediated radiosensitization correlated with reduced DNA-DSB repair, whereas BIBX1382BS did not impact DSB repair.

Conclusions:

  • Integrin-linked kinase (ILK) acts as a cell type-independent antisurvival factor in irradiated cells.
  • The radiosensitizing effects of ILK are critically dependent on functional EGFR tyrosine kinase (tk) activity.

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