Wagner, V.P., Martins, M.A.T., Martins, M.D. et al. (5 more authors) (2016) Overcoming adaptive resistance in mucoepidermoid carcinoma through inhibition of the IKK-β/IκBα/NFκB axis. Oncotarget, 7 (45). pp. 73032-73044. ISSN 1949-2553
Abstract
Patients with mucoepidermoid carcinoma (MEC) experience low survival rates and high morbidity following treatment, yet the intrinsic resistance of MEC cells to ionizing radiation (IR) and the mechanisms underlying acquired resistance remain unexplored. Herein, we demonstrated that low doses of IR intrinsically activated NFκB in resistant MEC cell lines. Moreover, resistance was significantly enhanced in IR-sensitive cell lines when NFκB pathway was stimulated. Pharmacological inhibition of the IKK-β/IκBα/ NFκB axis, using a single dose of FDA-approved Emetine, led to a striking sensitization of MEC cells to IR and a reduction in cancer stem cells. We achieved a major step towards better understanding the basic mechanisms involved in IR-adaptive resistance in MEC cell lines and how to efficiently overcome this critical problem.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2016 The author(s). Article is licensed under a Creative Commons Attribution 3.0 License. (https://creativecommons.org/licenses/by/3.0/) |
Keywords: | IKKα; cancer stem cells; irradiation; radio-adaptive; salivary cancer; Apoptosis; Biomarkers; Carcinoma, Mucoepidermoid; Cell Line, Tumor; Cell Survival; Gene Expression; Humans; I-kappa B Kinase; NF-kappa B; Neoplastic Stem Cells; Radiation Tolerance; Radiation, Ionizing; Signal Transduction |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Clinical Dentistry (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 17 Mar 2023 11:45 |
Last Modified: | 17 Mar 2023 11:45 |
Status: | Published |
Publisher: | Impact Journals, LLC |
Refereed: | Yes |
Identification Number: | 10.18632/oncotarget.12195 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:197450 |