{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T22:43:02Z","timestamp":1789684982765,"version":"4.0.1"},"reference-count":53,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2017,5,4]],"date-time":"2017-05-04T00:00:00Z","timestamp":1493856000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 CA140654"],"award-info":[{"award-number":["R01 CA140654"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2017,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Malignant mesothelioma is an aggressive cancer that is resistant to current therapy. The poor prognosis of mesothelioma has been associated with elevated Yes\u2010associated protein (YAP) activity. In this study, we evaluated the effect of targeting YAP in mesothelioma. First, we comprehensively studied YAP activity in five mesothelioma cell lines (211H, H2052, H290, MS\u20101 and H2452) and one normal mesothelial cell line (LP9). We found decreased phospho\u2010YAP to YAP protein ratio and consistently increased GTIIC reporter activity in 211H, H2052 and H290 compared to LP9. The same three cell lines (IC<jats:sub>50<\/jats:sub>s &lt; 1 \u03bcM) were more sensitive than LP9 (IC<jats:sub>50<\/jats:sub> = 3.5 \u03bcM) to the YAP\/TEAD inhibitor verteporfin. We also found that verteporfin significantly reduced YAP protein level, mRNA levels of YAP downstream genes and GTIIC reporter activity in the same three cell lines, indicating inhibition of YAP signaling by verteporfin. Verteporfin also impaired invasion and tumoursphere formation ability of H2052 and H290. To validate the effect of specific targeting YAP in mesothelioma cells, we down\u2010regulated YAP by siRNA. We found siYAP significantly decreased YAP transcriptional activity and impaired invasion and tumoursphere formation ability of H2052 and H290. Furthermore, forced overexpression of YAP rescued GTIIC reporter activity and cell viability after siYAP targeting 3\u2032UTR of YAP. Finally, we found concurrent immunohistochemistry staining of ROCK2 and YAP (<jats:italic>P<\/jats:italic> &lt; 0.05). Inhibition of ROCK2 decreased GTIIC reporter activity in H2052 and 211H suggesting that Rho\/ROCK signaling also contributed to YAP activation in mesothelioma cells. Our results indicate that YAP may be a potential therapeutic target in mesothelioma.<\/jats:p>","DOI":"10.1111\/jcmm.13182","type":"journal-article","created":{"date-parts":[[2017,5,4]],"date-time":"2017-05-04T07:36:49Z","timestamp":1493883409000},"page":"2663-2676","source":"Crossref","is-referenced-by-count":54,"title":["Targeting YAP in malignant pleural mesothelioma"],"prefix":"10.1111","volume":"21","author":[{"given":"Wen\u2010Qian","family":"Zhang","sequence":"first","affiliation":[{"name":"Thoracic Oncology Laboratory Department of Surgery, Comprehensive Cancer Center University of California San Francisco CA USA"},{"name":"Department of Thoracic Surgery Beijing Chao\u2010Yang Hospital Affiliated with Capital University of Medical Science Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8545-433X","authenticated-orcid":false,"given":"Yu\u2010Yuan","family":"Dai","sequence":"additional","affiliation":[{"name":"Thoracic 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Department of Surgery, Comprehensive Cancer Center University of California San Francisco CA USA"},{"name":"Department of Gastroenterology Shanghai General Hospital Shang Jiao Tong University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi\u2010Lin","family":"Yang","sequence":"additional","affiliation":[{"name":"Thoracic Oncology Laboratory Department of Surgery, Comprehensive Cancer Center University of California San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu\u2010Cheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Thoracic Oncology Laboratory Department of Surgery, Comprehensive Cancer Center University of California San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi\u2010Dong","family":"Xu","sequence":"additional","affiliation":[{"name":"Thoracic Oncology Laboratory Department of Surgery, Comprehensive Cancer Center University of California San 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