Dissociation of MIF-rpS3 Complex and Sequential NF-κB Activation Is Involved in IR-Induced Metastatic Conversion of NSCLC

HyeSook Youn, Beomseok Son, Wanyeon Kim, Se Young Jun, Jung Sub Lee, Jae Myung Lee, ChulHee Kang, Joon Kim, BuHyun Youn

Research output: Contribution to journalArticle

18 Citations (Scopus)

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. J. Cell. Biochem. 116: 2504-2516, 2015.

Original languageEnglish
Pages (from-to)2504-2516
Number of pages13
JournalJournal of Cellular Biochemistry
Volume116
Issue number11
DOIs
Publication statusPublished - 2015 Nov 1

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Ionizing radiation
Ionizing Radiation
Non-Small Cell Lung Carcinoma
Chemical activation
Cells
Neoplasm Metastasis
Tumors
Macrophage Migration-Inhibitory Factors
Epithelial-Mesenchymal Transition
Radiotherapy
ribosomal protein S3
Heterografts
Lung Neoplasms
Neoplasms
Genes
Cytokines
Inflammation
Gene Expression
Recurrence
Proteins

Keywords

  • METASTASIS
  • MIF
  • NF-κB
  • NON-SMALL CELL LUNG CANCER
  • rpS3

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Dissociation of MIF-rpS3 Complex and Sequential NF-κB Activation Is Involved in IR-Induced Metastatic Conversion of NSCLC. / Youn, HyeSook; Son, Beomseok; Kim, Wanyeon; Jun, Se Young; Lee, Jung Sub; Lee, Jae Myung; Kang, ChulHee; Kim, Joon; Youn, BuHyun.

In: Journal of Cellular Biochemistry, Vol. 116, No. 11, 01.11.2015, p. 2504-2516.

Research output: Contribution to journalArticle

Youn, HyeSook ; Son, Beomseok ; Kim, Wanyeon ; Jun, Se Young ; Lee, Jung Sub ; Lee, Jae Myung ; Kang, ChulHee ; Kim, Joon ; Youn, BuHyun. / Dissociation of MIF-rpS3 Complex and Sequential NF-κB Activation Is Involved in IR-Induced Metastatic Conversion of NSCLC. In: Journal of Cellular Biochemistry. 2015 ; Vol. 116, No. 11. pp. 2504-2516.
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AB - 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. J. Cell. Biochem. 116: 2504-2516, 2015.

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