{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T17:25:15Z","timestamp":1784913915833,"version":"3.55.0"},"reference-count":54,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,3,25]],"date-time":"2020-03-25T00:00:00Z","timestamp":1585094400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002850","name":"Fondo Nacional de Desarrollo Cient\u00edfico y Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["1171463"],"award-info":[{"award-number":["1171463"]}],"id":[{"id":"10.13039\/501100002850","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002850","name":"Fondo Nacional de Desarrollo Cient\u00edfico y Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["3140426"],"award-info":[{"award-number":["3140426"]}],"id":[{"id":"10.13039\/501100002850","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002850","name":"Fondo Nacional de Desarrollo Cient\u00edfico y Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["1170893"],"award-info":[{"award-number":["1170893"]}],"id":[{"id":"10.13039\/501100002850","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002850","name":"Fondo Nacional de Desarrollo Cient\u00edfico y Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["11180987"],"award-info":[{"award-number":["11180987"]}],"id":[{"id":"10.13039\/501100002850","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002850","name":"Fondo Nacional de Desarrollo Cient\u00edfico y Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["1181792"],"award-info":[{"award-number":["1181792"]}],"id":[{"id":"10.13039\/501100002850","id-type":"DOI","asserted-by":"publisher"}]},{"name":"CONICYT doctoral fellowship","award":["21140027"],"award-info":[{"award-number":["21140027"]}]},{"name":"European Union\u2019s Horizon 2020 Research and Innovation Programme","award":["825510"],"award-info":[{"award-number":["825510"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Gallbladder cancer is an aggressive disease with late diagnosis and no efficacious treatment. The Hippo-Yes-associated protein 1 (YAP1) signaling pathway has emerged as a target for the development of new therapeutic interventions in cancers. However, the role of the Hippo-targeted therapy has not been addressed in advanced gallbladder cancer (GBC). This study aimed to evaluate the expression of the major Hippo pathway components mammalian Ste20-like protein kinase 1 (MST1), YAP1 and transcriptional coactivator with PDZ-binding motif (TAZ) and examined the effects of Verteporfin (VP), a small molecular inhibitor of YAP1-TEA domain transcription factor (TEAD) protein interaction, in metastatic GBC cell lines and patient-derived organoids (PDOs). Immunohistochemical analysis revealed that advanced GBC patients had high nuclear expression of YAP1. High nuclear expression of YAP1 was associated with poor survival in GBC patients with subserosal invasion (pT2). Additionally, advanced GBC cases showed reduced expression of MST1 compared to chronic cholecystitis. Both VP treatment and YAP1 siRNA inhibited the migration ability in GBC cell lines. Interestingly, gemcitabine resistant PDOs with high nuclear expression of YAP1 were sensitive to VP treatment. Taken together, our results suggest that key components of the Hippo-YAP1 signaling pathway are dysregulated in advanced gallbladder cancer and reveal that the inhibition YAP1 may be a candidate for targeted therapy.<\/jats:p>","DOI":"10.3390\/cancers12040778","type":"journal-article","created":{"date-parts":[[2020,4,1]],"date-time":"2020-04-01T05:52:30Z","timestamp":1585720350000},"page":"778","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Hippo-YAP1 Is a Prognosis Marker and Potentially Targetable Pathway in Advanced Gallbladder Cancer"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3817-4896","authenticated-orcid":false,"given":"Patricia","family":"Garc\u00eda","sequence":"first","affiliation":[{"name":"Department of Pathology, School of Medicine, Pontificia Universidad Cat\u00f3lica de Chile, Santiago 8330024, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorena","family":"Rosa","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, Pontificia Universidad Cat\u00f3lica de Chile, Santiago 8330024, Chile"},{"name":"Applied Molecular and Cellular Biology PhD Program, Universidad de La Frontera, Temuco 4811230, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Vargas","sequence":"additional","affiliation":[{"name":"Department of Hematology Oncology, School of Medicine, Pontificia Universidad Cat\u00f3lica de Chile, Santiago 8331150, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helga","family":"Weber","sequence":"additional","affiliation":[{"name":"Centre of Excellence in Translational Medicine (CEMT) and Scientific and Technological Bioresource Nucleus (BIOREN), Universidad de la Frontera, Temuco 4810296, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaime A.","family":"Espinoza","sequence":"additional","affiliation":[{"name":"SciLifeLab, Division of Genome Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Solna, Stockholm 17165, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felipe","family":"Su\u00e1rez","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, Pontificia Universidad Cat\u00f3lica de Chile, Santiago 8330024, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Romero-Calvo","sequence":"additional","affiliation":[{"name":"Biomedical Visualization Graduate Program, Department of Biomedical and Health Information Sciences. College of Applied Health Sciences. University of Illinois at Chicago, Chicago, IL 60607, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Elgueta","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, Pontificia Universidad Cat\u00f3lica de Chile, Santiago 8330024, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Rivera","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, Pontificia Universidad Cat\u00f3lica de Chile, Santiago 8330024, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Nervi","sequence":"additional","affiliation":[{"name":"Department of Hematology Oncology, School of Medicine, Pontificia Universidad Cat\u00f3lica de Chile, Santiago 8331150, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javiera","family":"Obreque","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, Pontificia Universidad Cat\u00f3lica de Chile, Santiago 8330024, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela","family":"Leal","sequence":"additional","affiliation":[{"name":"Centre of Excellence in Translational Medicine (CEMT) and Scientific and Technological Bioresource Nucleus (BIOREN), Universidad de la Frontera, Temuco 4810296, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo","family":"Vi\u00f1uela","sequence":"additional","affiliation":[{"name":"Department of Digestive Surgery, Hepato-Bilio-Pancreatic Surgery Unit, Surgery Service, Complejo Asistencial Hospital Dr. S\u00f3tero del R\u00edo, Santiago 8207257, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloria","family":"Aguayo","sequence":"additional","affiliation":[{"name":"Department of Pathology, Complejo Asistencial Hospital Dr. S\u00f3tero del R\u00edo, Santiago 8207257, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Mu\u00f1iz","sequence":"additional","affiliation":[{"name":"Department of Hematology Oncology, School of Medicine, Pontificia Universidad Cat\u00f3lica de Chile, Santiago 8331150, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfredo","family":"Sagredo","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, Pontificia Universidad Cat\u00f3lica de Chile, Santiago 8330024, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8313-8774","authenticated-orcid":false,"given":"Juan C.","family":"Roa","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, Pontificia Universidad Cat\u00f3lica de Chile, Santiago 8330024, Chile"},{"name":"Millennium Institute on Immunology and Immunotherapy, Pontificia Universidad Cat\u00f3lica de Chile, Santiago 8331150, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5379-6191","authenticated-orcid":false,"given":"Carolina","family":"Bizama","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, Pontificia Universidad Cat\u00f3lica de Chile, Santiago 8330024, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,3,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1941","DOI":"10.1002\/ijc.31937","article-title":"Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods","volume":"144","author":"Ferlay","year":"2019","journal-title":"Int. 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