RIP1 Is a Novel Component of γ-ionizing Radiation-Induced Invasion of Non-Small Cell Lung Cancer Cells

Kang, A-Ram; Cho, Jeong Hyun; Lee, Na-Gyeong; Song, Jie-Young; Hwang, Sang-Gu; Lee, Dae-Hee; Um, Hong-Duck; Park, Jong Kuk

doi:10.3390/ijms21134584

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RIP1 Is a Novel Component of γ-ionizing Radiation-Induced Invasion of Non-Small Cell Lung Cancer Cells

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Division of Radiation Biomedical Research, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Korea

Department of Marine Food Science and Technology, Gangneung-Wonju National University, 120 Gangneung, Gangwon 210-702, Korea

Author to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Int. J. Mol. Sci. 2020, 21(13), 4584; https://doi.org/10.3390/ijms21134584

Received: 21 May 2020 / Revised: 10 June 2020 / Accepted: 24 June 2020 / Published: 28 June 2020

(This article belongs to the Special Issue Radiation and Tumor Microenvironment: Looking for Radio-Transmitted Signals)

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Abstract

Previously, we demonstrated that γ-ionizing radiation (IR) triggers the invasion/migration of A549 cells via activation of an EGFR–p38/ERK–STAT3/CREB-1–EMT pathway. Here, we have demonstrated the involvement of a novel intracellular signaling mechanism in γ-ionizing radiation (IR)-induced migration/invasion. Expression of receptor-interacting protein (RIP) 1 was initially increased upon exposure of A549, a non-small cell lung cancer (NSCLC) cell line, to IR. IR-induced RIP1 is located downstream of EGFR and involved in the expression/activity of matrix metalloproteases (MMP-2 and MMP-9) and vimentin, suggesting a role in epithelial-mesenchymal transition (EMT). Our experiments showed that IR-induced RIP1 sequentially induces Src-STAT3-EMT to promote invasion/migration. Inhibition of RIP1 kinase activity and expression blocked induction of EMT by IR and suppressed the levels and activities of MMP-2, MMP-9 and vimentin. IR-induced RIP1 activation was additionally associated with stimulation of the transcriptional factor NF-κB. Specifically, exposure to IR triggered NF-κB activation and inhibition of NF-κB suppressed IR-induced RIP1 expression, followed by a decrease in invasion/migration as well as EMT. Based on the collective results, we propose that IR concomitantly activates EGFR and NF-κB and subsequently triggers the RIP1–Src/STAT3–EMT pathway, ultimately promoting metastasis. View Full-Text

Keywords: signal transduction; γ-ionizing radiation; non-small cell lung cancer; cancer invasion; epithelial-mesenchymal transition; tumor microenvironment

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MDPI and ACS Style

Kang, A.-R.; Cho, J.H.; Lee, N.-G.; Song, J.-Y.; Hwang, S.-G.; Lee, D.-H.; Um, H.-D.; Park, J.K. RIP1 Is a Novel Component of γ-ionizing Radiation-Induced Invasion of Non-Small Cell Lung Cancer Cells. Int. J. Mol. Sci. 2020, 21, 4584. https://doi.org/10.3390/ijms21134584

AMA Style

Kang A-R, Cho JH, Lee N-G, Song J-Y, Hwang S-G, Lee D-H, Um H-D, Park JK. RIP1 Is a Novel Component of γ-ionizing Radiation-Induced Invasion of Non-Small Cell Lung Cancer Cells. International Journal of Molecular Sciences. 2020; 21(13):4584. https://doi.org/10.3390/ijms21134584

Chicago/Turabian Style

Kang, A-Ram, Jeong H. Cho, Na-Gyeong Lee, Jie-Young Song, Sang-Gu Hwang, Dae-Hee Lee, Hong-Duck Um, and Jong K. Park. 2020. "RIP1 Is a Novel Component of γ-ionizing Radiation-Induced Invasion of Non-Small Cell Lung Cancer Cells" International Journal of Molecular Sciences 21, no. 13: 4584. https://doi.org/10.3390/ijms21134584

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RIP1 Is a Novel Component of γ-ionizing Radiation-Induced Invasion of Non-Small Cell Lung Cancer Cells

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