title: Platelet-activating factor enhances tumour metastasis via the reactive oxygen species-dependent protein kinase casein kinase 2-mediated nuclear factor-κB activation.
abstract: Platelet-activating factor (PAF) promotes tumour metastasis via activation of the transcription factor nuclear factor-κB (NF-κB). We here investigated the role of the protein kinase CK2 (formerly Casein Kinase 2 or II) in PAF-induced NF-κB activation and tumour metastasis, given that PAF has been reported to increase CK2 activity, and that CK2 plays a key role in NF-κB activation. PAF increased CK2 activity, phosphorylation and protein expression in vivo as well as in vitro. CK2 inhibitors inhibited the PAF-mediated NF-κB activation and expression of NF-κB-dependent pro-inflammatory cytokines and anti-apoptotic factors. Pre-treatment with the antioxidant N-Acetyl-L-Cysteine (NAC) resulted in a significant inhibition in PAF-induced enhancement of CK2 activity, phosphorylation and protein expression in vivo as well as in vitro. H2 O2 and known reactive oxygen species inducers, lipopolysaccharide (LPS) and tumour necrosis factor-α (TNF-α) enhanced CK2 activity, phosphorylation and protein expression, which was again inhibited by antioxidant. PAF, LPS and TNF-α induced increased CK2 activity, phosphorylationand protein expression, which were inhibited by p38 inhibitor. PAF, LPS or TNF-α increased pulmonary metastasis of B16F10, which was inhibited by antioxidants, CK2 inhibitor and p38 inhibitor. Our data suggest that (i) reactive oxygen species activate CK2 via p38, which, in turn, induces NF-κB activation, and (ii) PAF, LPS and TNF-α increase pulmonary tumour metastasis via the induction of the reactive oxygen species (ROS)/p38/CK2/NF-κB pathway.
authors.affiliation: Department of Biological Sciences, College of Natural Sciences, Chonnam National University, Gwangju, Korea.
authors.forename: Kyoung-Jin
authors.initials: KJ
authors.lastname: Kim
authors.forename: Kyung-Deuk
authors.initials: KD
authors.lastname: Cho
authors.forename: Kyu Yun
authors.initials: KY
authors.lastname: Jang
authors.forename: Han-A
authors.initials: HA
authors.lastname: Kim
authors.forename: Hae-Kyoung
authors.initials: HK
authors.lastname: Kim
authors.forename: Hern-Ku
authors.initials: HK
authors.lastname: Lee
authors.forename: Suhn-Young
authors.initials: SY
authors.lastname: Im
mesh_terms: D000818:Animals; D015153:Blotting, Western; D047390:Casein Kinase II / Q000378:metabolism*; D004195:Disease Models, Animal; D024202:Electrophoretic Mobility Shift Assay; D004789:Enzyme Activation / Q000502:physiology; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000473:pathology; D010972:Platelet Activating Factor / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D016328:NF-kappa B; D010972:Platelet Activating Factor; D017382:Reactive Oxygen Species; D047390:Casein Kinase II
keywords: casein kinase 2; nuclear factor-κB; platelet-activating factor; reactive oxygen species; tumour metastasis