title: Integrin-linked kinase interacts with caspase-9 and -8 in an adhesion-dependent manner for promoting radiation-induced apoptosis in human leukemia cells.
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.
authors.affiliation: Bundeswehr Institute of Radiobiology, Munich, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Hess
authors.forename: D
authors.initials: D
authors.lastname: Estrugo
authors.forename: A
authors.initials: A
authors.lastname: Fischer
authors.forename: C
authors.initials: C
authors.lastname: Belka
authors.forename: N
authors.initials: N
authors.lastname: Cordes
mesh_terms: D017209:Apoptosis / Q000528:radiation effects*; D053181:Caspase 8 / Q000378:metabolism*; D053453:Caspase 9 / Q000378:metabolism*; D002448:Cell Adhesion; D005353:Fibronectins / Q000378:metabolism; D018922:HL-60 Cells; D006801:Humans; D019169:Jurkat Cells; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000494:pharmacology; D011836:Radiation Tolerance; D000099200:Scaffold Protein ILK
chemical_list: D053181:Caspase 8; D053453:Caspase 9; D005353:Fibronectins; D017346:Protein Serine-Threonine Kinases; D034741:RNA, Small Interfering; D000099200:Scaffold Protein ILK