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http://hdl.handle.net/2445/178608
Title: | Functional genomics screen identifies YAP1 as a key determinant to enhance treatment sensitivity in lung cancer cells |
Author: | Cheng, Haiying Zhang, Zhenfeng Rodriguez Barrueco, Ruth Borczuk, Alain Liu, Huijie Yu, Jiyang Silva, Jose M. Cheng, Simon K. Perez-Soler, Roman Halmos, Balazs |
Keywords: | Proteïnes Càncer Radiació Proteins Cancer Radiation |
Issue Date: | 17-May-2016 |
Publisher: | Impact Journals |
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. |
Note: | Reproducció del document publicat a: https://doi.org/10.18632/oncotarget.6721 |
It is part of: | Oncotarget, 2016, vol. 7, num. 20, p. 28976-28988 |
URI: | http://hdl.handle.net/2445/178608 |
Related resource: | https://doi.org/10.18632/oncotarget.6721 |
ISSN: | 1949-2553 |
Appears in Collections: | Articles publicats en revistes (Patologia i Terapèutica Experimental) |
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