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

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/...

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Autores principales: Kang, A-Ram, Cho, Jeong Hyun, Lee, Na-Gyeong, Song, Jie-Young, Hwang, Sang-Gu, Lee, Dae-Hee, Um, Hong-Duck, Park, Jong Kuk
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7369811/
https://www.ncbi.nlm.nih.gov/pubmed/32605153
http://dx.doi.org/10.3390/ijms21134584
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author Kang, A-Ram
Cho, Jeong Hyun
Lee, Na-Gyeong
Song, Jie-Young
Hwang, Sang-Gu
Lee, Dae-Hee
Um, Hong-Duck
Park, Jong Kuk
author_facet Kang, A-Ram
Cho, Jeong Hyun
Lee, Na-Gyeong
Song, Jie-Young
Hwang, Sang-Gu
Lee, Dae-Hee
Um, Hong-Duck
Park, Jong Kuk
author_sort Kang, A-Ram
collection PubMed
description 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.
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spelling pubmed-73698112020-07-21 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 Int J Mol Sci Article 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. MDPI 2020-06-28 /pmc/articles/PMC7369811/ /pubmed/32605153 http://dx.doi.org/10.3390/ijms21134584 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kang, A-Ram
Cho, Jeong Hyun
Lee, Na-Gyeong
Song, Jie-Young
Hwang, Sang-Gu
Lee, Dae-Hee
Um, Hong-Duck
Park, Jong Kuk
RIP1 Is a Novel Component of γ-ionizing Radiation-Induced Invasion of Non-Small Cell Lung Cancer Cells
title RIP1 Is a Novel Component of γ-ionizing Radiation-Induced Invasion of Non-Small Cell Lung Cancer Cells
title_full RIP1 Is a Novel Component of γ-ionizing Radiation-Induced Invasion of Non-Small Cell Lung Cancer Cells
title_fullStr RIP1 Is a Novel Component of γ-ionizing Radiation-Induced Invasion of Non-Small Cell Lung Cancer Cells
title_full_unstemmed RIP1 Is a Novel Component of γ-ionizing Radiation-Induced Invasion of Non-Small Cell Lung Cancer Cells
title_short RIP1 Is a Novel Component of γ-ionizing Radiation-Induced Invasion of Non-Small Cell Lung Cancer Cells
title_sort rip1 is a novel component of γ-ionizing radiation-induced invasion of non-small cell lung cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7369811/
https://www.ncbi.nlm.nih.gov/pubmed/32605153
http://dx.doi.org/10.3390/ijms21134584
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