{"doi":"10.1002/pbc.30774","title":"EZH2 is a key component of hepatoblastoma tumor cell growth","abstract":"BACKGROUND: 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-specific role in normal fetal liver development. EZH2 is overexpressed in hepatoblastoma (HB), an embryonal tumor. EZH2 can also promote tumorigenesis via a noncanonical, PRC2-independent mechanism via proto-oncogenic, direct protein interaction, including β-catenin. We hypothesize that the pathological activation of EZH2 contributes to HB propagation in a PRC2-independent manner. METHODS AND RESULTS: We demonstrate that EZH2 promotes proliferation in HB tumor-derived cell lines through interaction with β-catenin. Although aberrant EZH2 expression occurs, we determine that both canonical and noncanonical EZH2 signaling occurs based on specific gene-expression patterns and interaction with SUZ12, a PRC2 component, and β-catenin. Silencing and inhibition of EZH2 reduce primary HB cell proliferation. CONCLUSIONS: EZH2 overexpression promotes HB cell proliferation, with both canonical and noncanonical function detected. However, because EZH2 directly interacts with β-catenin 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.","journal":"Pediatric Blood & Cancer","year":2023,"id":352019,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9593,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":945140,"name":"Emily Schepers","orcid":"0000-0001-5567-262X","position":1,"is_corresponding":false},{"id":1097115,"name":"Harrison M. Zwolshen","orcid":"0009-0009-5246-5444","position":2,"is_corresponding":false},{"id":667549,"name":"Charissa Lake","orcid":"0000-0003-0731-7521","position":3,"is_corresponding":false},{"id":692821,"name":"Nikolai A. Timchenko","orcid":"0000-0003-4827-8274","position":4,"is_corresponding":false},{"id":301417,"name":"Rebekah Karns","orcid":"0000-0002-9720-4039","position":5,"is_corresponding":false},{"id":331828,"name":"Stefano Cairo","orcid":"0000-0002-4725-5970","position":6,"is_corresponding":false},{"id":342739,"name":"James I. Geller","orcid":"0000-0001-5181-116X","position":7,"is_corresponding":false},{"id":668484,"name":"Gregory M. Tiao","orcid":null,"position":8,"is_corresponding":false},{"id":668483,"name":"Alexander Bondoc","orcid":null,"position":9,"is_corresponding":false},{"id":667548,"name":"Kathryn Glaser","orcid":"0000-0002-0305-7489","position":0,"is_corresponding":true}],"reference_count":56,"raw_metadata":null,"created_at":"2026-07-19T01:12:45.897709Z","pmid":"37990130","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}