{"doi":"10.15252/embr.201948795","title":"PCAF‐mediated acetylation of ISX recruits BRD4 to promote epithelial‐mesenchymal transition","abstract":"Epigenetic regulation is important for cancer progression; however, the underlying mechanisms, particularly those involving protein acetylation, remain to be fully understood. Here, we show that p300/CBP-associated factor (PCAF)-dependent acetylation of the transcription factor intestine-specific homeobox (ISX) regulates epithelial-mesenchymal transition (EMT) and promotes cancer metastasis. Mechanistically, PCAF acetylation of ISX at lysine 69 promotes the interaction with acetylated bromodomain-containing protein 4 (BRD4) at lysine 332 in tumor cells, and the translocation of the resulting complex into the nucleus. There, it binds to promoters of EMT genes, where acetylation of histone 3 at lysines 9, 14, and 18 initiates chromatin remodeling and subsequent transcriptional activation. Ectopic ISX expression enhances EMT marker expression, including TWIST1, Snail1, and VEGF, induces cancer metastasis, but suppresses E-cadherin expression. In lung cancer, ectopic expression of PCAF-ISX-BRD4 axis components correlates with clinical metastatic features and poor prognosis. These results suggest that the PCAF-ISX-BRD4 axis mediates EMT signaling and regulates tumor initiation and metastasis.","journal":"EMBO Reports","year":2020,"id":91291,"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":45,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9537,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":458132,"name":"Kwei‐Yan Liu","orcid":null,"position":1,"is_corresponding":false},{"id":457237,"name":"W.Y. Jeng","orcid":"0000-0001-5870-587X","position":2,"is_corresponding":false},{"id":332357,"name":"Cheng‐Ming Chiang","orcid":"0000-0002-4968-3282","position":3,"is_corresponding":false},{"id":457238,"name":"Chee‐Yin Chai","orcid":"0000-0003-0486-9742","position":4,"is_corresponding":false},{"id":457239,"name":"Shyh‐Shin Chiou","orcid":"0000-0001-7639-9116","position":5,"is_corresponding":false},{"id":458133,"name":"Ming‐Shyang Huang","orcid":null,"position":6,"is_corresponding":false},{"id":457240,"name":"Kazunari K. Yokoyama","orcid":"0000-0001-8508-7587","position":7,"is_corresponding":false},{"id":457241,"name":"Shen‐Nien Wang","orcid":"0000-0002-4394-5608","position":8,"is_corresponding":false},{"id":458134,"name":"Shau‐Ku Huang","orcid":null,"position":9,"is_corresponding":false},{"id":458135,"name":"Shih‐Hsien Hsu","orcid":null,"position":10,"is_corresponding":false},{"id":457236,"name":"Li‐Ting Wang","orcid":"0000-0002-3335-8055","position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":null,"created_at":"2026-07-18T22:28:45.409789Z","pmid":"31908141","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":[]}