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dc.contributor.authorVisnes, Torkild
dc.contributor.authorBenítez-Buelga, Carlos
dc.contributor.authorCázares-Körner, Armando
dc.contributor.authorSanjiv, Kumar
dc.contributor.authorHanna, Bishoy M F
dc.contributor.authorMortusewicz, Oliver
dc.contributor.authorRajagopal, Varshni
dc.contributor.authorAlbers, Julian J
dc.contributor.authorHagey, Daniel W
dc.contributor.authorBekkhus, Tove
dc.contributor.authorEshtad, Saeed
dc.contributor.authorBaquero, Juan Miguel
dc.contributor.authorMasuyer, Geoffrey
dc.contributor.authorWallner, Olov
dc.contributor.authorMüller, Sarah
dc.contributor.authorPham, Therese
dc.contributor.authorGöktürk, Camilla
dc.contributor.authorRasti, Azita
dc.contributor.authorSuman, Sharda
dc.contributor.authorTorres-Ruiz Raul, Torres-Ruiz Raul 
dc.contributor.authorSarno, Antonio
dc.contributor.authorWiita, Elisée
dc.contributor.authorHoman, Evert J
dc.contributor.authorKarsten, Stella
dc.contributor.authorMarimuthu, Karthick
dc.contributor.authorMichel, Maurice
dc.contributor.authorKoolmeister, Tobias
dc.contributor.authorScobie, Martin
dc.contributor.authorLoseva, Olga
dc.contributor.authorAlmlöf, Ingrid
dc.contributor.authorUnterlass, Judith Edda
dc.contributor.authorPettke, Aleksandra
dc.contributor.authorBoström, Johan
dc.contributor.authorPandey, Monica
dc.contributor.authorGad, Helge
dc.contributor.authorHerr, Patrick
dc.contributor.authorJemth, Ann-Sofie
dc.contributor.authorEl Andaloussi, Samir
dc.contributor.authorKalderén, Christina
dc.contributor.authorRodriguez-Perales, Sandra
dc.contributor.authorBenítez, Javier
dc.contributor.authorKrokan, Hans E
dc.contributor.authorAltun, Mikael
dc.contributor.authorStenmark, Pål
dc.contributor.authorBerglund, Ulrika Warpman
dc.contributor.authorHelleday, Thomas
dc.contributor.authorRodriguez Perales, Sandra 
dc.contributor.authorEl Andaloussi, Samir
dc.identifier.citationNucleic Acids Res . 2020 ;48(21):12234-12251.es_ES
dc.description.abstractAltered oncogene expression in cancer cells causes loss of redox homeostasis resulting in oxidative DNA damage, e.g. 8-oxoguanine (8-oxoG), repaired by base excision repair (BER). PARP1 coordinates BER and relies on the upstream 8-oxoguanine-DNA glycosylase (OGG1) to recognise and excise 8-oxoG. Here we hypothesize that OGG1 may represent an attractive target to exploit reactive oxygen species (ROS) elevation in cancer. Although OGG1 depletion is well tolerated in non-transformed cells, we report here that OGG1 depletion obstructs A3 T-cell lymphoblastic acute leukemia growth in vitro and in vivo, validating OGG1 as a potential anti-cancer target. In line with this hypothesis, we show that OGG1 inhibitors (OGG1i) target a wide range of cancer cells, with a favourable therapeutic index compared to non-transformed cells. Mechanistically, OGG1i and shRNA depletion cause S-phase DNA damage, replication stress and proliferation arrest or cell death, representing a novel mechanistic approach to target cancer. This study adds OGG1 to the list of BER factors, e.g. PARP1, as potential targets for cancer treatment.es_ES
dc.description.sponsorshipS.R.P.'s laboratory is partially funded by funds from the Spanish National Research and Development Plan, Instituto de Salud Carlos III and FEDER [PI17/02303 to S.R.P]; R.T.R. is supported by a fellowship from the AECC scientific foundation; J.M.B. is supported by Spanish Ministry of Education, Culture and Sport [FPU15/01978]; J.B.'s laboratory is partially funded by FEDER funds, H2020 BRIDGES project and the Spanish Network on Rare Diseases (CIBERER) [FIS PI16/00440]; Faculty of Medicine at the Norwegian University of Science and Technology and the Central Norway Regional Health Authority supports [46056921 to A.S. and H.E.K.]; Svanhild and Arne Must's Fund for Medical Research (to A.S. and H.E.K.); Norwegian Research Council (to T.V.); SIN-TEF SEP project 102020885 (to T.V.); Vinnova (to A.C.K and P.S.); the Torsten and Ragnar Soderberg Foundation (to T.H.) and the Helleday Foundation (to C.B.). Funding for open access charge and project support: European Union's Horizon 2020 research and innovation programunder the Marie Sklodowska-Curie grant agreement [722729 to A.P., B.M.F.H., T.H.]; European Research Council [ERC TAROX-695376 to T.H.]; Swedish Research Council (to T.H. and P.S.); Swedish Cancer Society (to T.H. and P.S.); Swedish Children's Cancer Foundation (to T.H.); Swedish Pain Relief Foundation (to T.H.).es_ES
dc.relation.isversionofPublisher's versiones_ES
dc.subject.meshGene Expression Regulation, Neoplastic es_ES
dc.subject.meshAnimals es_ES
dc.subject.meshAntineoplastic Agents es_ES
dc.subject.meshCell Line, Tumor es_ES
dc.subject.meshCell Proliferation es_ES
dc.subject.meshColonic Neoplasms es_ES
dc.subject.meshDNA Damage es_ES
dc.subject.meshDNA Glycosylases es_ES
dc.subject.meshDNA Repair es_ES
dc.subject.meshDNA Replication es_ES
dc.subject.meshDNA, Neoplasm es_ES
dc.subject.meshEnzyme Inhibitors es_ES
dc.subject.meshGuanine es_ES
dc.subject.meshHCT116 Cells es_ES
dc.subject.meshHumans es_ES
dc.subject.meshMice es_ES
dc.subject.meshMice, Nude es_ES
dc.subject.meshMolecular Targeted Therapy es_ES
dc.subject.meshOxidative Stress es_ES
dc.subject.meshPoly (ADP-Ribose) Polymerase-1 es_ES
dc.subject.meshRNA, Small Interfering es_ES
dc.subject.meshReactive Oxygen Species es_ES
dc.subject.meshSignal Transduction es_ES
dc.subject.meshSurvival Analysis es_ES
dc.subject.meshTumor Burden es_ES
dc.subject.meshXenograft Model Antitumor Assays es_ES
dc.titleTargeting OGG1 arrests cancer cell proliferation by inducing replication stress.es_ES
dc.rights.licenseAtribución-NoComercial-CompartirIgual 4.0 Internacional*
dc.contributor.funderInstituto de Salud Carlos III - ISCIIIes_ES
dc.contributor.funderEuropean Union (EU)es_ES
dc.identifier.journalNucleic acids researches_ES
dc.repisalud.orgCNIOCNIO::Unidades técnicas::Unidad de Citogenética Moleculares_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/FIS PI16/00440es_ES

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Atribución-NoComercial-CompartirIgual 4.0 Internacional
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