{"doi":"10.1016/j.celrep.2022.111672","title":"Estrone, the major postmenopausal estrogen, binds ERa to induce SNAI2, epithelial-to-mesenchymal transition, and ER+ breast cancer metastasis","abstract":"Recent work showed that the dominant post-menopausal estrogen, estrone, cooperates with nuclear factor κB (NF-κB) to stimulate inflammation, while pre-menopausal 17β-estradiol opposes NF-κB. Here, we show that post-menopausal estrone, but not 17β-estradiol, activates epithelial-to-mesenchymal transition (EMT) genes to stimulate breast cancer metastasis. HSD17B14, which converts 17β-estradiol to estrone, is higher in cancer than normal breast tissue and in metastatic than primary cancers and associates with earlier metastasis. Treatment with estrone, but not 17β-estradiol, and HSD17B14 overexpression both stimulate an EMT, matrigel invasion, and lung, bone, and liver metastasis in estrogen-receptor-positive (ER+) breast cancer models, while HSD17B14 knockdown reverses the EMT. Estrone:ERα recruits CBP/p300 to the SNAI2 promoter to induce SNAI2 and stimulate an EMT, while 17β-estradiol:ERα recruits co-repressors HDAC1 and NCOR1 to this site. Present work reveals novel differences in gene regulation by these estrogens and the importance of estrone to ER+ breast cancer progression. Upon loss of 17β-estradiol at menopause, estrone-liganded ERα would promote ER+ breast cancer invasion and metastasis.","journal":"Cell Reports","year":2022,"id":243441,"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":34,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9515,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":269691,"name":"Manuel Picon‐Ruiz","orcid":"0000-0002-9427-0946","position":1,"is_corresponding":false},{"id":875789,"name":"Maiko Sho","orcid":null,"position":2,"is_corresponding":false},{"id":592918,"name":"Derek Van Booven","orcid":null,"position":3,"is_corresponding":false},{"id":272556,"name":"Vanessa Nunes de Paiva","orcid":null,"position":4,"is_corresponding":false},{"id":875790,"name":"Anna B. Diaz-Ruano","orcid":null,"position":5,"is_corresponding":false},{"id":269697,"name":"Tan A. Ince","orcid":"0000-0003-0315-6425","position":6,"is_corresponding":false},{"id":269703,"name":"Joyce M. Slingerland","orcid":"0000-0003-1487-8554","position":7,"is_corresponding":false},{"id":272555,"name":"Rehana Qureshi","orcid":null,"position":0,"is_corresponding":true}],"reference_count":79,"raw_metadata":null,"created_at":"2026-07-19T00:23:16.032700Z","pmid":"36384125","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":[]}