{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T09:20:49Z","timestamp":1790932849283,"version":"4.1.0"},"reference-count":26,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2011,10,20]],"date-time":"2011-10-20T00:00:00Z","timestamp":1319068800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2012,1]]},"abstract":"Abstract<\/jats:title>\n \n Background\/Aims<\/jats:title>\n \n Hepatocellular carcinoma (\n HCC<\/jats:styled-content>\n ), cholangiocarcinoma (\n CC<\/jats:styled-content>\n ) and hepatoblastoma (\n HB<\/jats:styled-content>\n ) are the main hepatic malignancies with limited treatment options and high mortality. Recent studies have implicated\n H<\/jats:styled-content>\n ippo kinase pathway in cancer development, but detailed analysis of\n H<\/jats:styled-content>\n ippo kinase signalling in human hepatic malignancies, especially\n CC<\/jats:styled-content>\n and\n HB<\/jats:styled-content>\n , is lacking.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We investigated\n H<\/jats:styled-content>\n ippo kinase signalling in\n HCC<\/jats:styled-content>\n ,\n CC<\/jats:styled-content>\n and\n HB<\/jats:styled-content>\n using cells and patient samples.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Increased expression of yes\u2010associated protein (\n Y<\/jats:styled-content>\n ap), the downstream effector of the\n H<\/jats:styled-content>\n ippo kinase pathway, was observed in\n HCC<\/jats:styled-content>\n cells, and si\n RNA<\/jats:styled-content>\n \u2010mediated knockdown of\n Y<\/jats:styled-content>\n ap resulted in decreased survival of\n HCC<\/jats:styled-content>\n cells. The density\u2010dependent activation of Hippo kinase pathway characteristic of normal cells was not observed in\n HCC<\/jats:styled-content>\n cells and\n CCLP<\/jats:styled-content>\n cells, a cholangiocarcinoma cell line. Immunohistochemistry of\n Y<\/jats:styled-content>\n ap in\n HCC<\/jats:styled-content>\n ,\n CC<\/jats:styled-content>\n and\n HB<\/jats:styled-content>\n tissues indicated extensive nuclear localization of\n Y<\/jats:styled-content>\n ap in majority of tissues. Western blot analysis performed using total cell extracts from patient samples and normal livers showed extensive activation of\n Y<\/jats:styled-content>\n ap. Marked induction of\n G<\/jats:styled-content>\n lypican\u20103,\n CTGF<\/jats:styled-content>\n and\n S<\/jats:styled-content>\n urvivin, the three\n Y<\/jats:styled-content>\n ap target genes was observed in the tumour samples. Further analysis revealed significant decrease in expression and activity of\n Lats<\/jats:styled-content>\n kinase, the main upstream regulator of\n Y<\/jats:styled-content>\n ap. However, no change in activation of\n Mst<\/jats:styled-content>\n \u20102 kinase, the upstream regulator of Lats kinase was observed.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n These data show that\n Y<\/jats:styled-content>\n ap induction mediated by inactivation of\n L<\/jats:styled-content>\n ats is observed in hepatic malignancies. These studies highlight\n H<\/jats:styled-content>\n ippo kinase pathway as a novel therapeutic target for hepatic malignancies.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/j.1478-3231.2011.02646.x","type":"journal-article","created":{"date-parts":[[2011,10,21]],"date-time":"2011-10-21T08:27:31Z","timestamp":1319185651000},"page":"38-47","source":"Crossref","is-referenced-by-count":134,"title":["Deregulation of Hippo kinase signalling in Human hepatic malignancies"],"prefix":"10.1111","volume":"32","author":[{"given":"Hua","family":"Li","sequence":"first","affiliation":[{"name":"Department of Pharmacology Toxicology and Therapeutics University of Kansas Medical Center Kansas City KS USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andy","family":"Wolfe","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Toxicology and Therapeutics University of Kansas Medical Center Kansas City KS USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seth","family":"Septer","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Children's Mercy Hospital Kansas City MO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genea","family":"Edwards","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Toxicology and Therapeutics University of Kansas Medical Center Kansas City KS USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobo","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Toxicology and Therapeutics University of Kansas Medical Center Kansas City KS USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmad","family":"Bashar Abdulkarim","sequence":"additional","affiliation":[{"name":"Department of Surgery University of Kansas Medical Center Kansas City KS USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarangarajan","family":"Ranganathan","sequence":"additional","affiliation":[{"name":"Department of Pathology Children's Hospital of Pittsburgh of UPMC Pittsburgh PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Udayan","family":"Apte","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Toxicology and Therapeutics University of Kansas Medical Center Kansas City KS USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,10,20]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/mpo.10180"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2002.33411"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1872-034X.2007.00192.x"},{"key":"e_1_2_7_5_1","first-page":"517","article-title":"Hepatocellular carcinoma \u2010 United States, 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