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Integrin-linked kinase interacts with caspase-9 and -8 in an adhesion-dependent manner for promoting radiation-induced apoptosis in human leukemia cells

Oncogene volume 26, pages 1372–1384 (2007)Cite this article

Abstract

Integrin-mediated adhesion of leukemia cells to extracellular matrix proteins reduces apoptosis following radiation-induced genotoxic injury. To evaluate the role of integrin-linked kinase (ILK) in this process, HL60 human acute promyelocytic leukemia cells were stably transfected with ILK wild-type or kinase-hyperactive overexpression vectors. Suspension or fibronectin (FN) adhesion cultures were irradiated with X-rays and processed for measurement of apoptosis, mitochondrial transmembrane potential and caspase activation. Adhesion to FN pronouncedly reduced radiation-induced apoptosis of HL60 cells and vector controls. Intriguingly, overexpressed ILK enhanced apoptosis after irradiation by combined activation of caspase-3 through caspase-8 and -9 in irradiated FN cultures. Irradiation of ILK suspension cultures lacked caspase-8 activation, but showed serial cleavage of caspase-9, -3 and poly (ADP-ribose) polymerase. These findings further characterize the cell death-promoting function of ILK in DNA-damaged cells. Moreover, ILK might represent a potential therapeutic target for innovative chemo- and radiooncological approaches in hematological malignancies.

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Acknowledgements

We thank Bärbel Reincke, Michaela Hiber, Gabriele Schröder, Monika Kraus and Daniela Tschuck for excellent technical assistance. We are indebted to Dr KM Yamada for providing mAb13 antibodies (NIDCR/NIH, Bethesda, MA) and Dr P Juo (Boston, MA) for the caspase-8-negative Jurkat cells. The work was funded in part by a grant from the Federal Ministry of Education and Research (BMBF-03ZIK041 to NC).

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Authors and Affiliations

  1. Bundeswehr Institute of Radiobiology, Munich, Germany

    F Hess, D Estrugo, A Fischer & N Cordes

  2. Department of Radiation Oncology, University Tübingen, Tübingen, Germany

    C Belka

  3. OncoRay – Radiation Research in Oncology, Medical Faculty Carl Gustav Carus, University of Technology Dresden, Dresden, Germany

    N Cordes

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  1. F Hess
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Correspondence to N Cordes.

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Hess, F., Estrugo, D., Fischer, A. et al. Integrin-linked kinase interacts with caspase-9 and -8 in an adhesion-dependent manner for promoting radiation-induced apoptosis in human leukemia cells. Oncogene 26, 1372–1384 (2007). https://doi.org/10.1038/sj.onc.1209947

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