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...
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| Veröffentlicht in: | Molecular therapy 2017-08, Vol.25 (8), p.1900-1916 |
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| creator | 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 |
| 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.
[Display omitted]
Oncolytic viruses offer a promising therapeutic approach to treat cancer. In this issue, Olagnier et al. demonstrate that the antioxidant compound sulforaphane activates the transcriptional regulator Nrf2, leading to suppression of the innate antiviral response, stimulation of autophagy, and enhancement of vesicular stomatitis virus-directed oncolysis of tumor cells. |
| doi_str_mv | 10.1016/j.ymthe.2017.04.022 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5542709</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S152500161730206X</els_id><sourcerecordid>2198009670</sourcerecordid><originalsourceid>FETCH-LOGICAL-c553t-a9e232f49b6322ffca0e3a7ed34700e742a38b8e1669a3ad7b282e5c379da7e33</originalsourceid><addsrcrecordid>eNp9UUuP0zAQjhCIfcAvQEKWOCf4EcfJAaRqgWWlFXsocLVcZ5K6SuxgO5Fy5J_jpaWCCyePx99jPF-WvSK4IJhUbw_FOsY9FBQTUeCywJQ-yS4JpzzHmJZPzzWpLrKrEA6pIrypnmcXtOZUCMous58bHc2ionEWuQ598R1FW9NbNRjbo83cj2BjQN8hGD0PyqNtdGOCR5Oaxs8BPVjthjWk-2JUYkQ37VW_5h-8WcCi7TxNHkI4GWxssjNeDehuHGdr4voie9apIcDL03mdffv08evN5_z-4fbuZnOfa85ZzFUDlNGubHYVo7TrtMLAlICWlQJjECVVrN7VQKqqUUy1YkdrClwz0bQJxth19v6oO827EVqd_pXGkJM3o_KrdMrIf1-s2cveLZLzkgrcJIE3JwHvfswQojy42adNBUlJU2PcVAInFDuitHcheOjODgTLx9zkQf7OTT7mJnEpU26J9frv4c6cP0ElwLsjANKKFgNeBm3AamiNBx1l68x_DX4BOlauZg</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2198009670</pqid></control><display><type>article</type><title>Activation of Nrf2 Signaling Augments Vesicular Stomatitis Virus Oncolysis via Autophagy-Driven Suppression of Antiviral Immunity</title><source>MEDLINE</source><source>EZB-FREE-00999 freely available EZB journals</source><source>ProQuest Central UK/Ireland</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><creator>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</creator><creatorcontrib>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</creatorcontrib><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.
[Display omitted]
Oncolytic viruses offer a promising therapeutic approach to treat cancer. In this issue, Olagnier et al. demonstrate that the antioxidant compound sulforaphane activates the transcriptional regulator Nrf2, leading to suppression of the innate antiviral response, stimulation of autophagy, and enhancement of vesicular stomatitis virus-directed oncolysis of tumor cells.</description><identifier>ISSN: 1525-0016</identifier><identifier>EISSN: 1525-0024</identifier><identifier>DOI: 10.1016/j.ymthe.2017.04.022</identifier><identifier>PMID: 28527723</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animal models ; Animals ; Antineoplastic Agents - pharmacology ; Antioxidants ; Antioxidants - pharmacology ; Apoptosis ; Autophagy ; Autophagy - drug effects ; cancer ; Cancer therapies ; Cell Line ; Clinical trials ; Combined Modality Therapy ; Disease Models, Animal ; Experiments ; Flow cytometry ; Grants ; Host-Pathogen Interactions - immunology ; Humans ; Immunity - drug effects ; Immunity, Innate - drug effects ; Infections ; innate antiviral response ; Interferon ; Isothiocyanates - pharmacology ; Lung cancer ; Medical research ; Mice ; Mice, Knockout ; Neoplasms - metabolism ; Neoplasms - mortality ; Neoplasms - pathology ; Neoplasms - therapy ; NF-E2-Related Factor 2 - genetics ; NF-E2-Related Factor 2 - metabolism ; Nrf2 ; Oncolysis ; Oncolytic Virotherapy ; Oncolytic Viruses - physiology ; Original ; Phagocytosis ; Prostate cancer ; Proteins ; Replication ; Sequence Deletion ; Signal Transduction - drug effects ; Stomatitis ; Studies ; Sulforaphane ; Sulfoxides ; Tumors ; Vesicular Stomatitis - immunology ; Vesicular Stomatitis - metabolism ; Vesicular Stomatitis - virology ; Vesicular stomatitis Indiana virus - drug effects ; Vesicular stomatitis Indiana virus - physiology ; Viral Matrix Proteins - genetics ; Virus Replication - drug effects ; Viruses ; VSV ; Xenografts</subject><ispartof>Molecular therapy, 2017-08, Vol.25 (8), p.1900-1916</ispartof><rights>2017 The Author(s)</rights><rights>Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.</rights><rights>2017. The Author(s)</rights><rights>2017 The Author(s) 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c553t-a9e232f49b6322ffca0e3a7ed34700e742a38b8e1669a3ad7b282e5c379da7e33</citedby><cites>FETCH-LOGICAL-c553t-a9e232f49b6322ffca0e3a7ed34700e742a38b8e1669a3ad7b282e5c379da7e33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5542709/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2198009670?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>230,315,728,781,785,886,27926,27927,53793,53795,64387,64391,72471</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28527723$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Olagnier, David</creatorcontrib><creatorcontrib>Lababidi, Rassin R.</creatorcontrib><creatorcontrib>Hadj, Samar Bel</creatorcontrib><creatorcontrib>Sze, Alexandre</creatorcontrib><creatorcontrib>Liu, Yiliu</creatorcontrib><creatorcontrib>Naidu, Sharadha Dayalan</creatorcontrib><creatorcontrib>Ferrari, Matteo</creatorcontrib><creatorcontrib>Jiang, Yuan</creatorcontrib><creatorcontrib>Chiang, Cindy</creatorcontrib><creatorcontrib>Beljanski, Vladimir</creatorcontrib><creatorcontrib>Goulet, Marie-Line</creatorcontrib><creatorcontrib>Knatko, Elena V.</creatorcontrib><creatorcontrib>Dinkova-Kostova, Albena T.</creatorcontrib><creatorcontrib>Hiscott, John</creatorcontrib><creatorcontrib>Lin, Rongtuan</creatorcontrib><title>Activation of Nrf2 Signaling Augments Vesicular Stomatitis Virus Oncolysis via Autophagy-Driven Suppression of Antiviral Immunity</title><title>Molecular therapy</title><addtitle>Mol Ther</addtitle><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.
[Display omitted]
Oncolytic viruses offer a promising therapeutic approach to treat cancer. In this issue, Olagnier et al. demonstrate that the antioxidant compound sulforaphane activates the transcriptional regulator Nrf2, leading to suppression of the innate antiviral response, stimulation of autophagy, and enhancement of vesicular stomatitis virus-directed oncolysis of tumor cells.</description><subject>Animal models</subject><subject>Animals</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Antioxidants</subject><subject>Antioxidants - pharmacology</subject><subject>Apoptosis</subject><subject>Autophagy</subject><subject>Autophagy - drug effects</subject><subject>cancer</subject><subject>Cancer therapies</subject><subject>Cell Line</subject><subject>Clinical trials</subject><subject>Combined Modality Therapy</subject><subject>Disease Models, Animal</subject><subject>Experiments</subject><subject>Flow cytometry</subject><subject>Grants</subject><subject>Host-Pathogen Interactions - immunology</subject><subject>Humans</subject><subject>Immunity - drug effects</subject><subject>Immunity, Innate - drug effects</subject><subject>Infections</subject><subject>innate antiviral response</subject><subject>Interferon</subject><subject>Isothiocyanates - pharmacology</subject><subject>Lung cancer</subject><subject>Medical research</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Neoplasms - metabolism</subject><subject>Neoplasms - mortality</subject><subject>Neoplasms - pathology</subject><subject>Neoplasms - therapy</subject><subject>NF-E2-Related Factor 2 - genetics</subject><subject>NF-E2-Related Factor 2 - metabolism</subject><subject>Nrf2</subject><subject>Oncolysis</subject><subject>Oncolytic Virotherapy</subject><subject>Oncolytic Viruses - physiology</subject><subject>Original</subject><subject>Phagocytosis</subject><subject>Prostate cancer</subject><subject>Proteins</subject><subject>Replication</subject><subject>Sequence Deletion</subject><subject>Signal Transduction - drug effects</subject><subject>Stomatitis</subject><subject>Studies</subject><subject>Sulforaphane</subject><subject>Sulfoxides</subject><subject>Tumors</subject><subject>Vesicular Stomatitis - immunology</subject><subject>Vesicular Stomatitis - metabolism</subject><subject>Vesicular Stomatitis - virology</subject><subject>Vesicular stomatitis Indiana virus - drug effects</subject><subject>Vesicular stomatitis Indiana virus - physiology</subject><subject>Viral Matrix Proteins - genetics</subject><subject>Virus Replication - drug effects</subject><subject>Viruses</subject><subject>VSV</subject><subject>Xenografts</subject><issn>1525-0016</issn><issn>1525-0024</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9UUuP0zAQjhCIfcAvQEKWOCf4EcfJAaRqgWWlFXsocLVcZ5K6SuxgO5Fy5J_jpaWCCyePx99jPF-WvSK4IJhUbw_FOsY9FBQTUeCywJQ-yS4JpzzHmJZPzzWpLrKrEA6pIrypnmcXtOZUCMous58bHc2ionEWuQ598R1FW9NbNRjbo83cj2BjQN8hGD0PyqNtdGOCR5Oaxs8BPVjthjWk-2JUYkQ37VW_5h-8WcCi7TxNHkI4GWxssjNeDehuHGdr4voie9apIcDL03mdffv08evN5_z-4fbuZnOfa85ZzFUDlNGubHYVo7TrtMLAlICWlQJjECVVrN7VQKqqUUy1YkdrClwz0bQJxth19v6oO827EVqd_pXGkJM3o_KrdMrIf1-s2cveLZLzkgrcJIE3JwHvfswQojy42adNBUlJU2PcVAInFDuitHcheOjODgTLx9zkQf7OTT7mJnEpU26J9frv4c6cP0ElwLsjANKKFgNeBm3AamiNBx1l68x_DX4BOlauZg</recordid><startdate>20170802</startdate><enddate>20170802</enddate><creator>Olagnier, David</creator><creator>Lababidi, Rassin R.</creator><creator>Hadj, Samar Bel</creator><creator>Sze, Alexandre</creator><creator>Liu, Yiliu</creator><creator>Naidu, Sharadha Dayalan</creator><creator>Ferrari, Matteo</creator><creator>Jiang, Yuan</creator><creator>Chiang, Cindy</creator><creator>Beljanski, Vladimir</creator><creator>Goulet, Marie-Line</creator><creator>Knatko, Elena V.</creator><creator>Dinkova-Kostova, Albena T.</creator><creator>Hiscott, John</creator><creator>Lin, Rongtuan</creator><general>Elsevier Inc</general><general>Elsevier Limited</general><general>American Society of Gene & Cell Therapy</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>5PM</scope></search><sort><creationdate>20170802</creationdate><title>Activation of Nrf2 Signaling Augments Vesicular Stomatitis Virus Oncolysis via Autophagy-Driven Suppression of Antiviral Immunity</title><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></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c553t-a9e232f49b6322ffca0e3a7ed34700e742a38b8e1669a3ad7b282e5c379da7e33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Animal models</topic><topic>Animals</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Antioxidants</topic><topic>Antioxidants - pharmacology</topic><topic>Apoptosis</topic><topic>Autophagy</topic><topic>Autophagy - drug effects</topic><topic>cancer</topic><topic>Cancer therapies</topic><topic>Cell Line</topic><topic>Clinical trials</topic><topic>Combined Modality Therapy</topic><topic>Disease Models, Animal</topic><topic>Experiments</topic><topic>Flow cytometry</topic><topic>Grants</topic><topic>Host-Pathogen Interactions - immunology</topic><topic>Humans</topic><topic>Immunity - drug effects</topic><topic>Immunity, Innate - drug effects</topic><topic>Infections</topic><topic>innate antiviral response</topic><topic>Interferon</topic><topic>Isothiocyanates - pharmacology</topic><topic>Lung cancer</topic><topic>Medical research</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Neoplasms - metabolism</topic><topic>Neoplasms - mortality</topic><topic>Neoplasms - pathology</topic><topic>Neoplasms - therapy</topic><topic>NF-E2-Related Factor 2 - genetics</topic><topic>NF-E2-Related Factor 2 - metabolism</topic><topic>Nrf2</topic><topic>Oncolysis</topic><topic>Oncolytic Virotherapy</topic><topic>Oncolytic Viruses - physiology</topic><topic>Original</topic><topic>Phagocytosis</topic><topic>Prostate cancer</topic><topic>Proteins</topic><topic>Replication</topic><topic>Sequence Deletion</topic><topic>Signal Transduction - drug effects</topic><topic>Stomatitis</topic><topic>Studies</topic><topic>Sulforaphane</topic><topic>Sulfoxides</topic><topic>Tumors</topic><topic>Vesicular Stomatitis - immunology</topic><topic>Vesicular Stomatitis - metabolism</topic><topic>Vesicular Stomatitis - virology</topic><topic>Vesicular stomatitis Indiana virus - drug effects</topic><topic>Vesicular stomatitis Indiana virus - physiology</topic><topic>Viral Matrix Proteins - genetics</topic><topic>Virus Replication - drug effects</topic><topic>Viruses</topic><topic>VSV</topic><topic>Xenografts</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Olagnier, David</creatorcontrib><creatorcontrib>Lababidi, Rassin R.</creatorcontrib><creatorcontrib>Hadj, Samar Bel</creatorcontrib><creatorcontrib>Sze, Alexandre</creatorcontrib><creatorcontrib>Liu, Yiliu</creatorcontrib><creatorcontrib>Naidu, Sharadha Dayalan</creatorcontrib><creatorcontrib>Ferrari, Matteo</creatorcontrib><creatorcontrib>Jiang, Yuan</creatorcontrib><creatorcontrib>Chiang, Cindy</creatorcontrib><creatorcontrib>Beljanski, Vladimir</creatorcontrib><creatorcontrib>Goulet, Marie-Line</creatorcontrib><creatorcontrib>Knatko, Elena V.</creatorcontrib><creatorcontrib>Dinkova-Kostova, Albena T.</creatorcontrib><creatorcontrib>Hiscott, John</creatorcontrib><creatorcontrib>Lin, Rongtuan</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>ProQuest Health and Medical</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>ProQuest Biological Science Journals</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Molecular therapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Olagnier, David</au><au>Lababidi, Rassin R.</au><au>Hadj, Samar Bel</au><au>Sze, Alexandre</au><au>Liu, Yiliu</au><au>Naidu, Sharadha Dayalan</au><au>Ferrari, Matteo</au><au>Jiang, Yuan</au><au>Chiang, Cindy</au><au>Beljanski, Vladimir</au><au>Goulet, Marie-Line</au><au>Knatko, Elena V.</au><au>Dinkova-Kostova, Albena T.</au><au>Hiscott, John</au><au>Lin, Rongtuan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Activation of Nrf2 Signaling Augments Vesicular Stomatitis Virus Oncolysis via Autophagy-Driven Suppression of Antiviral Immunity</atitle><jtitle>Molecular therapy</jtitle><addtitle>Mol Ther</addtitle><date>2017-08-02</date><risdate>2017</risdate><volume>25</volume><issue>8</issue><spage>1900</spage><epage>1916</epage><pages>1900-1916</pages><issn>1525-0016</issn><eissn>1525-0024</eissn><abstract>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.
[Display omitted]
Oncolytic viruses offer a promising therapeutic approach to treat cancer. In this issue, Olagnier et al. demonstrate that the antioxidant compound sulforaphane activates the transcriptional regulator Nrf2, leading to suppression of the innate antiviral response, stimulation of autophagy, and enhancement of vesicular stomatitis virus-directed oncolysis of tumor cells.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>28527723</pmid><doi>10.1016/j.ymthe.2017.04.022</doi><tpages>17</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1525-0016 |
| ispartof | Molecular therapy, 2017-08, Vol.25 (8), p.1900-1916 |
| issn | 1525-0016 1525-0024 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5542709 |
| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; ProQuest Central UK/Ireland; PubMed Central; Alma/SFX Local Collection |
| subjects | Animal models Animals Antineoplastic Agents - pharmacology Antioxidants Antioxidants - pharmacology Apoptosis Autophagy Autophagy - drug effects cancer Cancer therapies Cell Line Clinical trials Combined Modality Therapy Disease Models, Animal Experiments Flow cytometry Grants Host-Pathogen Interactions - immunology Humans Immunity - drug effects Immunity, Innate - drug effects Infections innate antiviral response Interferon Isothiocyanates - pharmacology Lung cancer Medical research Mice Mice, Knockout Neoplasms - metabolism Neoplasms - mortality Neoplasms - pathology Neoplasms - therapy NF-E2-Related Factor 2 - genetics NF-E2-Related Factor 2 - metabolism Nrf2 Oncolysis Oncolytic Virotherapy Oncolytic Viruses - physiology Original Phagocytosis Prostate cancer Proteins Replication Sequence Deletion Signal Transduction - drug effects Stomatitis Studies Sulforaphane Sulfoxides Tumors Vesicular Stomatitis - immunology Vesicular Stomatitis - metabolism Vesicular Stomatitis - virology Vesicular stomatitis Indiana virus - drug effects Vesicular stomatitis Indiana virus - physiology Viral Matrix Proteins - genetics Virus Replication - drug effects Viruses VSV Xenografts |
| title | Activation of Nrf2 Signaling Augments Vesicular Stomatitis Virus Oncolysis via Autophagy-Driven Suppression of Antiviral Immunity |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-17T19%3A53%3A51IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Activation%20of%20Nrf2%20Signaling%20Augments%20Vesicular%20Stomatitis%20Virus%20Oncolysis%20via%20Autophagy-Driven%20Suppression%20of%20Antiviral%20Immunity&rft.jtitle=Molecular%20therapy&rft.au=Olagnier,%20David&rft.date=2017-08-02&rft.volume=25&rft.issue=8&rft.spage=1900&rft.epage=1916&rft.pages=1900-1916&rft.issn=1525-0016&rft.eissn=1525-0024&rft_id=info:doi/10.1016/j.ymthe.2017.04.022&rft_dat=%3Cproquest_pubme%3E2198009670%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2198009670&rft_id=info:pmid/28527723&rft_els_id=S152500161730206X&rfr_iscdi=true |