{"doi":"10.1038/onc.2012.390","title":"EZH2 promotes a bi-lineage identity in basal-like breast cancer cells","abstract":"The mechanisms regulating breast cancer differentiation state are poorly understood. Of particular interest are molecular regulators controlling the highly aggressive and poorly differentiated traits of basal-like breast carcinomas. Here we show that the Polycomb factor EZH2 maintains the differentiation state of basal-like breast cancer cells, and promotes the expression of progenitor associated and basal-lineage genes. Specifically, EZH2 regulates the composition of basal-like breast cancer cell populations by promoting a ‘bi-lineage’ differentiation state, in which cells co-express basal- and luminal-lineage markers. We show that human basal-like breast cancers contain a subpopulation of bi-lineage cells, and that EZH2-deficient cells give rise to tumors with a decreased proportion of such cells. Bi-lineage cells express genes that are active in normal luminal progenitors, and possess increased colony-formation capacity, consistent with a primitive differentiation state. We found that GATA3, a driver of luminal differentiation, performs a function opposite to EZH2, acting to suppress bi-lineage identity and luminal-progenitor gene expression. GATA3 levels increase upon EZH2 silencing, mediating a decrease in bi-lineage cell numbers. Our findings reveal a novel role for EZH2 in controlling basal-like breast cancer differentiation state and intra-tumoral cell composition.","journal":"Oncogene","year":2012,"id":3573,"datarank":2.3922887654461507,"base_score":3.6375861597263857,"endowment":3.6375861597263857,"self_citation_contribution":0.5456379239589579,"citation_network_contribution":1.8466508414871927,"self_endowment_contribution":0.5456379239589579,"citer_contribution":1.8466508414871927,"corpus_percentile":null,"corpus_rank":null,"citation_count":37,"citer_count":35,"citers_with_citation_signal":31,"citers_with_endowment":31,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.0464,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2012-09-17","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":36951,"name":"T Hadar","orcid":null,"position":2,"is_corresponding":false},{"id":36952,"name":"Y. Karamansha","orcid":null,"position":3,"is_corresponding":false},{"id":36953,"name":"L Liberman","orcid":null,"position":4,"is_corresponding":false},{"id":36954,"name":"I Waldhorn","orcid":null,"position":5,"is_corresponding":false},{"id":52961,"name":"Irit Gat-Viks","orcid":null,"position":6,"is_corresponding":false},{"id":36956,"name":"B Maly","orcid":null,"position":8,"is_corresponding":false},{"id":36957,"name":"M Darash-Yahana","orcid":null,"position":9,"is_corresponding":false},{"id":32334,"name":"Ittai Ben-Porath","orcid":null,"position":11,"is_corresponding":false},{"id":32319,"name":"Roy Z. Granit","orcid":"0000-0002-6487-2559","position":12,"is_corresponding":false},{"id":32323,"name":"Yael Gabai","orcid":null,"position":13,"is_corresponding":false},{"id":36960,"name":"Tal Hadar","orcid":null,"position":14,"is_corresponding":false},{"id":36961,"name":"Louisa M. Liberman","orcid":"0000-0002-1315-0097","position":15,"is_corresponding":false},{"id":36962,"name":"Ithai Waldhorn","orcid":null,"position":16,"is_corresponding":false},{"id":36963,"name":"Irit Gat‐Viks","orcid":"0000-0002-5431-6444","position":17,"is_corresponding":false},{"id":29633,"name":"Prisca Liberali","orcid":"0000-0003-0695-6081","position":18,"is_corresponding":false},{"id":36964,"name":"Bella Maly","orcid":null,"position":19,"is_corresponding":false},{"id":36965,"name":"Merav Darash‐Yahana","orcid":null,"position":20,"is_corresponding":false},{"id":32331,"name":"Tamar Peretz","orcid":"0000-0001-8016-4010","position":21,"is_corresponding":false},{"id":32335,"name":"Ittai Ben‐Porath","orcid":"0000-0001-7815-1165","position":22,"is_corresponding":false}],"reference_count":44,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-03-01T18:20:47.508186Z","pmid":null,"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":[]}