{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T03:57:30Z","timestamp":1791863850214,"version":"4.3.4"},"reference-count":56,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,11,21]],"date-time":"2023-11-21T00:00:00Z","timestamp":1700524800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["P30 DK078392"],"award-info":[{"award-number":["P30 DK078392"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Enhancer of zeste homolog 2 (EZH2) catalyzes the trimethylation of histone H3 at lysine 27 via the polycomb recessive complex 2 (PRC2) and plays a time\u2010specific role in normal fetal liver development. EZH2 is overexpressed in hepatoblastoma (HB), an embryonal tumor. EZH2 can also promote tumorigenesis via a noncanonical, PRC2\u2010independent mechanism via proto\u2010oncogenic, direct protein interaction, including \u03b2\u2010catenin. We hypothesize that the pathological activation of EZH2 contributes to HB propagation in a PRC2\u2010independent manner.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>We demonstrate that EZH2 promotes proliferation in HB tumor\u2010derived cell lines through interaction with \u03b2\u2010catenin. Although aberrant EZH2 expression occurs, we determine that both canonical and noncanonical EZH2 signaling occurs based on specific gene\u2010expression patterns and interaction with SUZ12, a PRC2 component, and \u03b2\u2010catenin. Silencing and inhibition of EZH2 reduce primary HB cell proliferation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>EZH2 overexpression promotes HB cell proliferation, with both canonical and noncanonical function detected. However, because EZH2 directly interacts with \u03b2\u2010catenin in human tumors and EZH2 overexpression is not equal to SUZ12, it seems that a noncanonical mechanism is contributing to HB pathogenesis. Further mechanistic studies are necessary to elucidate potential pathogenic downstream mechanisms and translational potential of EZH2 inhibitors for the treatment of HB.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.30774","type":"journal-article","created":{"date-parts":[[2023,11,23]],"date-time":"2023-11-23T23:34:21Z","timestamp":1700782461000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["EZH2 is a key component of hepatoblastoma tumor cell growth"],"prefix":"10.1002","volume":"71","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0305-7489","authenticated-orcid":false,"given":"Kathryn","family":"Glaser","sequence":"first","affiliation":[{"name":"Division of Pediatric General and Thoracic Surgery Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily J.","family":"Schepers","sequence":"additional","affiliation":[{"name":"Division 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