Cho, J.H.; Kang, A.; Lee, N.; Song, J.; Hwang, S.; Lee, D.; Um, H.; Park, J.K. RIP1 is Novel Component of γ-Ionizing Radiation-Induced Invasion of Non-Small Cell Lung Cancer Cells. Preprints2020, 2020010252. https://doi.org/10.20944/preprints202001.0252.v1
APA Style
Cho, J.H., Kang, A., Lee, N., Song, J., Hwang, S., Lee, D., Um, H., & Park, J.K. (2020). RIP1 is Novel Component of γ-Ionizing Radiation-Induced Invasion of Non-Small Cell Lung Cancer Cells. Preprints. https://doi.org/10.20944/preprints202001.0252.v1
Chicago/Turabian Style
Cho, J.H., Hong-Duck Um and Jong Kuk Park. 2020 "RIP1 is Novel Component of γ-Ionizing Radiation-Induced Invasion of Non-Small Cell Lung Cancer Cells" Preprints. https://doi.org/10.20944/preprints202001.0252.v1
Abstract
Previously, we demonstrated that 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.
Keywords
signal transduction; γ-ionizing radiation; cancer invasion; non-small cell lung cancer; epithelial-mesenchymal transition; tumor microenvironment
Subject
Medicine and Pharmacology, Oncology and Oncogenics
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
,
,
,
,
*
