{"doi":"10.1016/j.celrep.2023.112821","title":"High FOXA1 levels induce ER transcriptional reprogramming, a pro-metastatic secretome, and metastasis in endocrine-resistant breast cancer","abstract":"Aberrant activation of the forkhead protein FOXA1 is observed in advanced hormone-related cancers. However, the key mediators of high FOXA1 signaling remain elusive. We demonstrate that ectopic high FOXA1 (H-FOXA1) expression promotes estrogen receptor-positive (ER+) breast cancer (BC) metastasis in a xenograft mouse model. Mechanistically, H-FOXA1 reprograms ER-chromatin binding to elicit a core gene signature (CGS) enriched in ER+ endocrine-resistant (EndoR) cells. We identify Secretome14, a CGS subset encoding ER-dependent cancer secretory proteins, as a strong predictor for poor outcomes of ER+ BC. It is elevated in ER+ metastases vs. primary tumors, irrespective of ESR1 mutations. Genomic ER binding near Secretome14 genes is also increased in mutant ER-expressing or mitogen-treated ER+ BC cells and in ER+ metastatic vs. primary tumors, suggesting a convergent pathway including high growth factor receptor signaling in activating pro-metastatic secretome genes. Our findings uncover H-FOXA1-induced ER reprogramming that drives EndoR and metastasis partly via an H-FOXA1/ER-dependent secretome.","journal":"Cell Reports","year":2023,"id":328675,"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":22,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9457,"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":639739,"name":"Resel Pereira","orcid":null,"position":1,"is_corresponding":false},{"id":380019,"name":"Chia-Chia Liu","orcid":null,"position":2,"is_corresponding":false},{"id":263245,"name":"Carmine De Angelis","orcid":"0000-0003-1158-4630","position":3,"is_corresponding":false},{"id":709519,"name":"Martin J. Shea","orcid":null,"position":4,"is_corresponding":false},{"id":639740,"name":"Sarmistha Nanda","orcid":null,"position":5,"is_corresponding":false},{"id":639741,"name":"Lanfang Qin","orcid":null,"position":6,"is_corresponding":false},{"id":709518,"name":"Tamika Mitchell","orcid":null,"position":7,"is_corresponding":false},{"id":639738,"name":"Maria Letizia Cataldo","orcid":null,"position":8,"is_corresponding":false},{"id":379128,"name":"Jamunarani Veeraraghavan","orcid":"0000-0002-9524-9487","position":9,"is_corresponding":false},{"id":638874,"name":"Vidyalakshmi Sethunath","orcid":"0000-0002-3308-3063","position":10,"is_corresponding":false},{"id":379367,"name":"Mario Giuliano","orcid":"0000-0003-0835-3153","position":11,"is_corresponding":false},{"id":379371,"name":"Carolina Gutiérrez","orcid":"0000-0002-2941-3461","position":12,"is_corresponding":false},{"id":311112,"name":"Balázs Győrffy","orcid":"0000-0002-5772-3766","position":13,"is_corresponding":false},{"id":708904,"name":"Meghana V. Trivedi","orcid":"0000-0002-0585-5580","position":14,"is_corresponding":false},{"id":3739,"name":"Ofir Cohen","orcid":"0000-0002-0043-6838","position":15,"is_corresponding":false},{"id":3754,"name":"Nikhil Wagle","orcid":"0000-0003-3332-9438","position":16,"is_corresponding":false},{"id":574767,"name":"Agostina Nardone","orcid":"0000-0003-3277-1101","position":17,"is_corresponding":false},{"id":565777,"name":"Rinath Jeselsohn","orcid":"0000-0001-7996-7529","position":18,"is_corresponding":false},{"id":270275,"name":"Mothaffar F. Rimawi","orcid":"0000-0002-4284-5656","position":19,"is_corresponding":false},{"id":44719,"name":"C. Kent Osborne","orcid":"0000-0002-0044-618X","position":20,"is_corresponding":false},{"id":263252,"name":"Rachel Schiff","orcid":"0000-0003-1696-5213","position":21,"is_corresponding":false},{"id":263244,"name":"Xiaoyong Fu","orcid":"0000-0003-0005-6496","position":0,"is_corresponding":true}],"reference_count":103,"raw_metadata":null,"created_at":"2026-07-19T01:08:56.940647Z","pmid":"37467106","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":[]}