Targeting the centriolar replication factor STIL synergizes with DNA damaging agents for treatment of ovarian cancer

Rabinowicz, Noa et al.

Detalles Bibliográficos
Autores: Rabinowicz, Noa, Checa-Rodríguez, Cintia, Huertas Sánchez, Pablo, Izraeli, Shai
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2017
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/165678
Acceso en línea:http://hdl.handle.net/10261/165678
Access Level:acceso abierto
Palabra clave:Ovarian cancer
Genomic instability
Centrosomes
DNA damage
STIL
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spelling Targeting the centriolar replication factor STIL synergizes with DNA damaging agents for treatment of ovarian cancerRabinowicz, NoaCheca-Rodríguez, CintiaHuertas Sánchez, PabloIzraeli, ShaiOvarian cancerGenomic instabilityCentrosomesDNA damageSTILRabinowicz, Noa et al.Advanced ovarian cancer is an incurable disease. Thus, novel therapies are required. We wished to identify new therapeutic targets for ovarian cancer. ShRNA screen performed in 42 ovarian cancer cell lines identified the centriolar replication factor STIL as an essential gene for ovarian cancer cells. This was verified in-vivo in orthotopic human ovarian cancer mouse models. STIL depletion by administration of siRNA in neutral liposomes resulted in robust anti-tumor effect that was further enhanced in combination with cisplatin. Consistent with this finding, STIL depletion enhanced the extent of DNA double strand breaks caused by DNA damaging agents. This was associated with centrosomal depletion, ongoing genomic instability and enhanced formation of micronuclei. Interestingly, the ongoing DNA damage was not associated with reduced DNA repair. Indeed, we observed that depletion of STIL enhanced canonical homologous recombination repair and increased BRCA1 and RAD51 foci in response to DNA double strand breaks. Thus, inhibition of STIL significantly enhances the efficacy of DNA damaging chemotherapeutic drugs in treatment of ovarian cancer.This research was supported by grant OC100237 from USA Department of Defense (to S. Izraeli and A.K. Sood), by SINF (S. Izraeli and A.K. Sood), Israel Science Foundation ICORE program (S. Izraeli, A. Levy-Barda), Israel Cancer Research Foundation (N. Rabinowicz) and Israel Ministry of Science/German Cancer Research Center (S. Izraeli), Israel Ministry of Commerce “Nofar” program (SI), The Giorgio and Dora Shapiro Chair for Hematological Malignancies (SI), NIH grants (CA083639, CA098258, UH2 TR000943, and CA016672 for A.K. Sood), the RGK Foundation (A.K. Sood), the Frank McGraw Memorial Chair in Cancer Research and the American Cancer Society Research Professor Award (A.K. Sood), grants from the Regional Government of Andalucia (P12-BIO-515, P. Huertas), the Spanish Ministry of Economy and Competitivity (SAF2013-43255-P, P. Huertas) and the European Research Council (DSBRECA, P. Huertas).Peer ReviewedNature Publishing GroupIsrael Science FoundationIsrael Cancer Research FundDeutsches KrebsforschungszentrumFederal Ministry of Education and Research (Germany)National Institutes of Health (US)RGK FoundationAmerican Cancer SocietyJunta de AndalucíaMinisterio de Economía y Competitividad (España)European Research CouncilDepartment of Defense (US)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2018201820172018info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/165678reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/EC/FP7/278867info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2013-43255-Phttps://doi.org/10.18632/oncotarget.16068Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/1656782026-05-22T06:33:51Z
dc.title.none.fl_str_mv Targeting the centriolar replication factor STIL synergizes with DNA damaging agents for treatment of ovarian cancer
title Targeting the centriolar replication factor STIL synergizes with DNA damaging agents for treatment of ovarian cancer
spellingShingle Targeting the centriolar replication factor STIL synergizes with DNA damaging agents for treatment of ovarian cancer
Rabinowicz, Noa
Ovarian cancer
Genomic instability
Centrosomes
DNA damage
STIL
title_short Targeting the centriolar replication factor STIL synergizes with DNA damaging agents for treatment of ovarian cancer
title_full Targeting the centriolar replication factor STIL synergizes with DNA damaging agents for treatment of ovarian cancer
title_fullStr Targeting the centriolar replication factor STIL synergizes with DNA damaging agents for treatment of ovarian cancer
title_full_unstemmed Targeting the centriolar replication factor STIL synergizes with DNA damaging agents for treatment of ovarian cancer
title_sort Targeting the centriolar replication factor STIL synergizes with DNA damaging agents for treatment of ovarian cancer
dc.creator.none.fl_str_mv Rabinowicz, Noa
Checa-Rodríguez, Cintia
Huertas Sánchez, Pablo
Izraeli, Shai
author Rabinowicz, Noa
author_facet Rabinowicz, Noa
Checa-Rodríguez, Cintia
Huertas Sánchez, Pablo
Izraeli, Shai
author_role author
author2 Checa-Rodríguez, Cintia
Huertas Sánchez, Pablo
Izraeli, Shai
author2_role author
author
author
dc.contributor.none.fl_str_mv Israel Science Foundation
Israel Cancer Research Fund
Deutsches Krebsforschungszentrum
Federal Ministry of Education and Research (Germany)
National Institutes of Health (US)
RGK Foundation
American Cancer Society
Junta de Andalucía
Ministerio de Economía y Competitividad (España)
European Research Council
Department of Defense (US)
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Ovarian cancer
Genomic instability
Centrosomes
DNA damage
STIL
topic Ovarian cancer
Genomic instability
Centrosomes
DNA damage
STIL
description Rabinowicz, Noa et al.
publishDate 2017
dc.date.none.fl_str_mv 2017
2018
2018
2018
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/165678
url http://hdl.handle.net/10261/165678
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/EC/FP7/278867
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2013-43255-P
https://doi.org/10.18632/oncotarget.16068
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
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