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Activation of Nrf2 Signaling Augments Vesicular Stomatitis Virus Oncolysis via Autophagy-Driven Suppression of Antiviral Immunity
Oncolytic viruses (OVs) offer a promising therapeutic approach to treat multiple types of cancer. In this study, we show that the manipulation of the antioxidant network via transcription factor Nrf2 augments vesicular stomatitis virus Δ51 (VSVΔ51) replication and sensitizes cancer cells to viral on...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society of Gene & Cell Therapy
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5542709/ https://www.ncbi.nlm.nih.gov/pubmed/28527723 http://dx.doi.org/10.1016/j.ymthe.2017.04.022 |
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author | Olagnier, David Lababidi, Rassin R. Hadj, Samar Bel Sze, Alexandre Liu, Yiliu Naidu, Sharadha Dayalan Ferrari, Matteo Jiang, Yuan Chiang, Cindy Beljanski, Vladimir Goulet, Marie-Line Knatko, Elena V. Dinkova-Kostova, Albena T. Hiscott, John Lin, Rongtuan |
author_facet | Olagnier, David Lababidi, Rassin R. Hadj, Samar Bel Sze, Alexandre Liu, Yiliu Naidu, Sharadha Dayalan Ferrari, Matteo Jiang, Yuan Chiang, Cindy Beljanski, Vladimir Goulet, Marie-Line Knatko, Elena V. Dinkova-Kostova, Albena T. Hiscott, John Lin, Rongtuan |
author_sort | Olagnier, David |
collection | PubMed |
description | Oncolytic viruses (OVs) offer a promising therapeutic approach to treat multiple types of cancer. In this study, we show that the manipulation of the antioxidant network via transcription factor Nrf2 augments vesicular stomatitis virus Δ51 (VSVΔ51) replication and sensitizes cancer cells to viral oncolysis. Activation of Nrf2 signaling by the antioxidant compound sulforaphane (SFN) leads to enhanced VSVΔ51 spread in OV-resistant cancer cells and improves the therapeutic outcome in different murine syngeneic and xenograft tumor models. Chemoresistant A549 lung cancer cells that display constitutive dominant hyperactivation of Nrf2 signaling are particularly vulnerable to VSVΔ51 oncolysis. Mechanistically, enhanced Nrf2 signaling stimulated viral replication in cancer cells and disrupted the type I IFN response via increased autophagy. This study reveals a previously unappreciated role for Nrf2 in the regulation of autophagy and the innate antiviral response that complements the therapeutic potential of VSV-directed oncolysis against multiple types of OV-resistant or chemoresistant cancer. |
format | Online Article Text |
id | pubmed-5542709 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | American Society of Gene & Cell Therapy |
record_format | MEDLINE/PubMed |
spelling | pubmed-55427092018-08-02 Activation of Nrf2 Signaling Augments Vesicular Stomatitis Virus Oncolysis via Autophagy-Driven Suppression of Antiviral Immunity Olagnier, David Lababidi, Rassin R. Hadj, Samar Bel Sze, Alexandre Liu, Yiliu Naidu, Sharadha Dayalan Ferrari, Matteo Jiang, Yuan Chiang, Cindy Beljanski, Vladimir Goulet, Marie-Line Knatko, Elena V. Dinkova-Kostova, Albena T. Hiscott, John Lin, Rongtuan Mol Ther Original Article Oncolytic viruses (OVs) offer a promising therapeutic approach to treat multiple types of cancer. In this study, we show that the manipulation of the antioxidant network via transcription factor Nrf2 augments vesicular stomatitis virus Δ51 (VSVΔ51) replication and sensitizes cancer cells to viral oncolysis. Activation of Nrf2 signaling by the antioxidant compound sulforaphane (SFN) leads to enhanced VSVΔ51 spread in OV-resistant cancer cells and improves the therapeutic outcome in different murine syngeneic and xenograft tumor models. Chemoresistant A549 lung cancer cells that display constitutive dominant hyperactivation of Nrf2 signaling are particularly vulnerable to VSVΔ51 oncolysis. Mechanistically, enhanced Nrf2 signaling stimulated viral replication in cancer cells and disrupted the type I IFN response via increased autophagy. This study reveals a previously unappreciated role for Nrf2 in the regulation of autophagy and the innate antiviral response that complements the therapeutic potential of VSV-directed oncolysis against multiple types of OV-resistant or chemoresistant cancer. American Society of Gene & Cell Therapy 2017-08-02 2017-05-17 /pmc/articles/PMC5542709/ /pubmed/28527723 http://dx.doi.org/10.1016/j.ymthe.2017.04.022 Text en © 2017 The Author(s) http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Original Article Olagnier, David Lababidi, Rassin R. Hadj, Samar Bel Sze, Alexandre Liu, Yiliu Naidu, Sharadha Dayalan Ferrari, Matteo Jiang, Yuan Chiang, Cindy Beljanski, Vladimir Goulet, Marie-Line Knatko, Elena V. Dinkova-Kostova, Albena T. Hiscott, John Lin, Rongtuan Activation of Nrf2 Signaling Augments Vesicular Stomatitis Virus Oncolysis via Autophagy-Driven Suppression of Antiviral Immunity |
title | Activation of Nrf2 Signaling Augments Vesicular Stomatitis Virus Oncolysis via Autophagy-Driven Suppression of Antiviral Immunity |
title_full | Activation of Nrf2 Signaling Augments Vesicular Stomatitis Virus Oncolysis via Autophagy-Driven Suppression of Antiviral Immunity |
title_fullStr | Activation of Nrf2 Signaling Augments Vesicular Stomatitis Virus Oncolysis via Autophagy-Driven Suppression of Antiviral Immunity |
title_full_unstemmed | Activation of Nrf2 Signaling Augments Vesicular Stomatitis Virus Oncolysis via Autophagy-Driven Suppression of Antiviral Immunity |
title_short | Activation of Nrf2 Signaling Augments Vesicular Stomatitis Virus Oncolysis via Autophagy-Driven Suppression of Antiviral Immunity |
title_sort | activation of nrf2 signaling augments vesicular stomatitis virus oncolysis via autophagy-driven suppression of antiviral immunity |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5542709/ https://www.ncbi.nlm.nih.gov/pubmed/28527723 http://dx.doi.org/10.1016/j.ymthe.2017.04.022 |
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