{"doi":"10.1101/2023.10.30.564775","title":"FoxA1/2-dependent epigenomic reprogramming drives lineage switching in lung adenocarcinoma","abstract":"ABSTRACT The ability of cancer cells to alter their identity is essential for tumor survival and progression. Loss of the pulmonary lineage specifier NKX2-1 within KRAS-driven lung adenocarcinoma (LUAD) enhances tumor progression and results in a pulmonary-to-gastric lineage switch that is dependent upon the activity of pioneer factors FoxA1 and FoxA2; however, the underlying mechanism remains largely unknown. Here, we show that FoxA1/2 reprogram the epigenetic landscape of NKX2-1-negative LUAD to facilitate a gastric identity. After Nkx2-1 deletion, FoxA1/2 mediate demethylation of gastric-defining genes through recruitment of TET3, an enzyme that induces DNA demethylation. H3K27ac ChIP-seq and HiChIP show that FoxA1/2 also control the activity of regulatory elements and their 3D interactions at gastric loci. Furthermore, oncogenic KRAS is required for the FoxA1/2-dependent epigenetic reprogramming. This work demonstrates the role of FoxA1/2 in rewiring the methylation and histone landscape and cis-regulatory dynamics of NKX2-1-negative LUAD to drive cancer cell lineage switching.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":392713,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9494,"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":859400,"name":"Walter A. Orellana","orcid":"0000-0003-4109-021X","position":1,"is_corresponding":false},{"id":1166287,"name":"Emily Wilson","orcid":"0000-0003-4350-6012","position":2,"is_corresponding":false},{"id":422538,"name":"Timothy J. Parnell","orcid":"0000-0002-3632-3691","position":3,"is_corresponding":false},{"id":670067,"name":"Gabriela Fort","orcid":null,"position":4,"is_corresponding":false},{"id":1166288,"name":"Headtlove Essel Dadzie","orcid":"0000-0002-2108-7956","position":5,"is_corresponding":false},{"id":571178,"name":"Xiaoyang Zhang","orcid":"0000-0002-0031-0290","position":6,"is_corresponding":false},{"id":71716,"name":"Eric L. Snyder","orcid":"0000-0003-3591-3195","position":7,"is_corresponding":false},{"id":1166704,"name":"Katherine Gillis","orcid":null,"position":0,"is_corresponding":true}],"reference_count":60,"raw_metadata":null,"created_at":"2026-07-19T01:18:56.730121Z","pmid":"37961260","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":[]}