Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/178608
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dc.contributor.authorCheng, Haiying-
dc.contributor.authorZhang, Zhenfeng-
dc.contributor.authorRodriguez Barrueco, Ruth-
dc.contributor.authorBorczuk, Alain-
dc.contributor.authorLiu, Huijie-
dc.contributor.authorYu, Jiyang-
dc.contributor.authorSilva, Jose M.-
dc.contributor.authorCheng, Simon K.-
dc.contributor.authorPerez-Soler, Roman-
dc.contributor.authorHalmos, Balazs-
dc.date.accessioned2021-06-21T17:17:42Z-
dc.date.available2021-06-21T17:17:42Z-
dc.date.issued2016-05-17-
dc.identifier.issn1949-2553-
dc.identifier.urihttp://hdl.handle.net/2445/178608-
dc.description.abstractSurvival for lung cancer patients remains dismal and is largely attributed to treatment resistance. To identify novel target genes the modulation of which could modify platinum resistance, we performed a high-throughput RNAi screen and identified Yes-associated protein (YAP1), a transcription coactivator and a known oncogene, as a potential actionable candidate. YAP1 ablation significantly improved sensitivities not only to cisplatin but also to ionizing radiation, both of which are DNA-damaging interventions, in non-small cell lung cancer (NSCLC) cells. Overall YAP1 was expressed in 75% of NSCLC specimens, whereas nuclear YAP1 which is the active form was present in 45% of 124 resected NSCLC. Interestingly, EGFR-mutated or KRAS-mutated NSCLC were associated with higher nuclear YAP1 staining in comparison to EGFR/KRAS wild-type. Relevantly, YAP1 downregulation improved sensitivity to erlotinib, an EGFR inhibitor. A pharmacological inhibitor of YAP1 signaling, verteporfin also synergized with cisplatin, radiation and erlotinib in NSCLC cells by potentiating cisplatin and radiation-related double-stranded breaks and decreasing expression of YAP1 and EGFR. Taken together, our study is the first to indicate the potential role of YAP1 as a common modulator of resistance mechanisms and a potential novel, actionable target that can improve responses to platinum, radiation and EGFR-targeted therapy in lung cancer.-
dc.format.extent13 p.-
dc.format.mimetypeapplication/pdf-
dc.language.isoeng-
dc.publisherImpact Journals-
dc.relation.isformatofReproducció del document publicat a: https://doi.org/10.18632/oncotarget.6721-
dc.relation.ispartofOncotarget, 2016, vol. 7, num. 20, p. 28976-28988-
dc.relation.urihttps://doi.org/10.18632/oncotarget.6721-
dc.rightscc-by (c) Cheng, Haiying et al., 2016-
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/-
dc.subject.classificationProteïnes-
dc.subject.classificationCàncer-
dc.subject.classificationRadiació-
dc.subject.otherProteins-
dc.subject.otherCancer-
dc.subject.otherRadiation-
dc.titleFunctional genomics screen identifies YAP1 as a key determinant to enhance treatment sensitivity in lung cancer cells-
dc.typeinfo:eu-repo/semantics/article-
dc.typeinfo:eu-repo/semantics/publishedVersion-
dc.identifier.idgrec694922-
dc.date.updated2021-06-21T17:17:42Z-
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess-
dc.identifier.pmid26716514-
Appears in Collections:Articles publicats en revistes (Patologia i Terapèutica Experimental)

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