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http://hdl.handle.net/2445/178608
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DC Field | Value | Language |
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dc.contributor.author | Cheng, Haiying | - |
dc.contributor.author | Zhang, Zhenfeng | - |
dc.contributor.author | Rodriguez Barrueco, Ruth | - |
dc.contributor.author | Borczuk, Alain | - |
dc.contributor.author | Liu, Huijie | - |
dc.contributor.author | Yu, Jiyang | - |
dc.contributor.author | Silva, Jose M. | - |
dc.contributor.author | Cheng, Simon K. | - |
dc.contributor.author | Perez-Soler, Roman | - |
dc.contributor.author | Halmos, Balazs | - |
dc.date.accessioned | 2021-06-21T17:17:42Z | - |
dc.date.available | 2021-06-21T17:17:42Z | - |
dc.date.issued | 2016-05-17 | - |
dc.identifier.issn | 1949-2553 | - |
dc.identifier.uri | http://hdl.handle.net/2445/178608 | - |
dc.description.abstract | Survival 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.extent | 13 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Impact Journals | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.18632/oncotarget.6721 | - |
dc.relation.ispartof | Oncotarget, 2016, vol. 7, num. 20, p. 28976-28988 | - |
dc.relation.uri | https://doi.org/10.18632/oncotarget.6721 | - |
dc.rights | cc-by (c) Cheng, Haiying et al., 2016 | - |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | - |
dc.source | Articles publicats en revistes (Patologia i Terapèutica Experimental) | - |
dc.subject.classification | Proteïnes | - |
dc.subject.classification | Càncer | - |
dc.subject.classification | Radiació | - |
dc.subject.other | Proteins | - |
dc.subject.other | Cancer | - |
dc.subject.other | Radiation | - |
dc.title | Functional genomics screen identifies YAP1 as a key determinant to enhance treatment sensitivity in lung cancer cells | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.identifier.idgrec | 694922 | - |
dc.date.updated | 2021-06-21T17:17:42Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 26716514 | - |
Appears in Collections: | Articles publicats en revistes (Patologia i Terapèutica Experimental) |
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File | Description | Size | Format | |
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694922.pdf | 1.8 MB | Adobe PDF | View/Open |
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