{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T16:02:24Z","timestamp":1784563344767,"version":"3.55.0"},"reference-count":38,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T00:00:00Z","timestamp":1759881600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100015724","name":"Mayo Clinic Center for Cell Signaling in Gastroenterology","doi-asserted-by":"publisher","award":["P30DK084567"],"award-info":[{"award-number":["P30DK084567"]}],"id":[{"id":"10.13039\/100015724","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015724","name":"Mayo Clinic Center for Cell Signaling in Gastroenterology","doi-asserted-by":"publisher","award":["5P30 CA15083-43C1"],"award-info":[{"award-number":["5P30 CA15083-43C1"]}],"id":[{"id":"10.13039\/100015724","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015724","name":"Mayo Clinic Center for Cell Signaling in Gastroenterology","doi-asserted-by":"publisher","award":["P50 CA210964"],"award-info":[{"award-number":["P50 CA210964"]}],"id":[{"id":"10.13039\/100015724","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Mayo Clinic Medical Genome Facility\u2014Proteomics Core","award":["P30DK084567"],"award-info":[{"award-number":["P30DK084567"]}]},{"name":"Mayo Clinic Medical Genome Facility\u2014Proteomics Core","award":["5P30 CA15083-43C1"],"award-info":[{"award-number":["5P30 CA15083-43C1"]}]},{"name":"Mayo Clinic Medical Genome Facility\u2014Proteomics Core","award":["P50 CA210964"],"award-info":[{"award-number":["P50 CA210964"]}]},{"name":"Mayo Clinic Hepatobiliary SPORE","award":["P30DK084567"],"award-info":[{"award-number":["P30DK084567"]}]},{"name":"Mayo Clinic Hepatobiliary SPORE","award":["5P30 CA15083-43C1"],"award-info":[{"award-number":["5P30 CA15083-43C1"]}]},{"name":"Mayo Clinic Hepatobiliary SPORE","award":["P50 CA210964"],"award-info":[{"award-number":["P50 CA210964"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Lacking effective therapeutics, cholangiocarcinoma (CCA) remains a deadly malignancy of the biliary tract. The Hippo pathway effector protein Yes-associated protein (YAP) is implicated in CCA pathogenesis and chemotherapeutic resistance; however, the oncogenic mechanisms underlying YAP regulation remain incompletely understood. An enhanced understanding of YAP and its role in CCA may uncover novel therapeutic targets and better define resistance pathways. Human CCA cells and murine syngeneic CCA models were utilized to explore the molecular relationship of YAP and protein tyrosine phosphatase 1B (PTP1B). Previous work in CCA has demonstrated that YAP interacts with multiple protein tyrosine phosphatases, including SHP2 and PTP1B. We observed that PTP1B pharmacologic inhibition was associated with increased cell proliferation and YAP target gene expression, while genetically enforced overexpression of PTP1B was associated with a decrease in YAP activation. Treatment of CCA cells in vitro and syngeneic, orthotopically implanted CCA murine tumors in vivo with standard cytotoxic chemotherapy, gemcitabine\/cisplatin, had enhanced efficacy in the setting of PTP1B overexpression. These findings demonstrate that pYAPY357 can be modulated through protein tyrosine 1B phosphatase activity, and reducing pYAPY357 through enhanced phosphatase levels can sensitize CCA to chemotherapy.<\/jats:p>","DOI":"10.3390\/cells14191560","type":"journal-article","created":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T12:04:52Z","timestamp":1759925092000},"page":"1560","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Protein Tyrosine Phosphatase 1B Modulates the Activation of Yes-Associated Protein and Sensitizes to Cytotoxic Chemotherapy in Preclinical Models of Cholangiocarcinoma"],"prefix":"10.3390","volume":"14","author":[{"given":"Ryan D.","family":"Watkins","sequence":"first","affiliation":[{"name":"Department of Surgery, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0909-3165","authenticated-orcid":false,"given":"Jennifer L.","family":"Tomlinson","sequence":"additional","affiliation":[{"name":"Department of Surgery, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"EeeLN H.","family":"Buckarma","sequence":"additional","affiliation":[{"name":"Department of Surgery, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hendrien","family":"Kuipers","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle M.","family":"Carlson","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan W.","family":"Werneburg","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel R.","family":"O\u2019Brien","sequence":"additional","affiliation":[{"name":"Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rory L.","family":"Smoot","sequence":"additional","affiliation":[{"name":"Department of Surgery, Mayo Clinic, Rochester, MN 55905, USA"},{"name":"Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1053\/j.gastro.2013.10.013","article-title":"Pathogenesis, diagnosis, and management of cholangiocarcinoma","volume":"145","author":"Rizvi","year":"2013","journal-title":"Gastroenterology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1038\/nrclinonc.2017.157","article-title":"Cholangiocarcinoma\u2014Evolving concepts and therapeutic strategies","volume":"15","author":"Rizvi","year":"2018","journal-title":"Nat. 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