title: Dissociation of MIF-rpS3 complex and sequential NF-κB activation is involved in IR-induced metastatic conversion of NSCLC.
abstract: Frequent relapse and spreading of tumors during radiotherapy are principal obstacles to treatment of non-small cell lung cancer (NSCLC). In this study, we aimed to investigate how macrophage migration inhibitory factor (MIF) which is expressed at high levels in metastatic and primary lung cancer cells could regulate NSCLC metastasis in response to ionizing radiation (IR). The results indicated that MIF and ribosomal protein S3 (rpS3) were shown to be connected to inflammation, proliferation, and metastasis of NSCLC via IR-induced activation of the NF-κB pathway. Under unirradiated conditions, MIF physically established a complex with rpS3. MIF-rpS3 dissociation induced by IR activated NF-κB and made the expression of target genes of this factor transactivated in two NSCLC cell lines, A549, and NCI-H358. We also found that IR-induced dissociation of this complex led to increased secretion of pro-inflammatory cytokines and modulated the expression of epithelial-mesenchymal transition marker proteins. Finally, the effects of IR-induced dissociation of the MIF-rpS3 complex on tumor metastasis were confirmed by in vivo xenograft studies. Taken together, the present study revealed that dissociation of the MIF-rpS3 complex and subsequent activation of NF-κB is a critical post-IR exposure event that accounts for IR-induced metastatic conversion of NSCLC.
authors.affiliation: Department of Biological Sciences, Pusan National University, Busan, 609-735, Republic of Korea.|Nuclear Science Research Institute, Pusan National University, Busan, 609-735, Republic of Korea.
authors.forename: HyeSook
authors.initials: H
authors.lastname: Youn
authors.affiliation: Department of Integrated Biological Science, Pusan National University, Busan, 609-735, Republic of Korea.
authors.forename: Beomseok
authors.initials: B
authors.lastname: Son
authors.affiliation: Department of Biological Sciences, Pusan National University, Busan, 609-735, Republic of Korea.|Nuclear Science Research Institute, Pusan National University, Busan, 609-735, Republic of Korea.
authors.forename: Wanyeon
authors.initials: W
authors.lastname: Kim
authors.affiliation: Department of Chemistry, Washington State University, Pullman, WA 99164, USA.
authors.forename: Se Young
authors.initials: SY
authors.lastname: Jun
authors.affiliation: Department of Orthopaedic Surgery, Medical Research Institute, Pusan National University School of Medicine, Busan, 602-739, Republic of Korea.
authors.forename: Jung Sub
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Department of Naval Architecture and Ocean Engineering, Pusan National University, Busan, 609-735, Republic of Korea.
authors.forename: Jae-Myung
authors.initials: JM
authors.lastname: Lee
authors.affiliation: Department of Chemistry, Washington State University, Pullman, WA 99164, USA.
authors.forename: ChulHee
authors.initials: C
authors.lastname: Kang
authors.affiliation: Laboratory of Biochemistry, School of Life Sciences & Biotechnology, Korea University, Seoul, 136-701, Republic of Korea.
authors.forename: Joon
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences, Pusan National University, Busan, 609-735, Republic of Korea.|Nuclear Science Research Institute, Pusan National University, Busan, 609-735, Republic of Korea.|Department of Integrated Biological Science, Pusan National University, Busan, 609-735, Republic of Korea.
authors.forename: BuHyun
authors.initials: B
authors.lastname: Youn
mesh_terms: D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition / Q000528:radiation effects; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000378:metabolism*; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D008263:Macrophage Migration-Inhibitory Factors / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D011485:Protein Binding / Q000528:radiation effects; D011839:Radiation, Ionizing; D012269:Ribosomal Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000528:radiation effects
chemical_list: D008263:Macrophage Migration-Inhibitory Factors; D016328:NF-kappa B; C578290:RPS3 protein, human; D012269:Ribosomal Proteins; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human
keywords: METASTASIS; MIF; NF-κB; NON-SMALL CELL LUNG CANCER; rpS3