{"doi":"10.1101/gad.353142.125","title":"Lineage rewiring in lung adenocarcinoma via HNF4α and NKX2-1 dynamics","abstract":"<jats:p>Lineage plasticity drives treatment resistance in lung adenocarcinoma (LUAD) as cancer cells adopt new identities. In this issue of <jats:italic>Genes &amp; Development</jats:italic>, Fort and colleagues (doi:10.1101/gad.352742.125) report HNF4α as a key regulator of hybrid identity states and tumor progression in NKX2-1-positive LUAD. Using murine and human models, they show that HNF4α promotes gastrointestinal/liver-like programs and suppresses pulmonary identity by modulating cell identity-specific binding of NKX2-1. In addition, RAS/MEK signaling was implicated in maintenance of this hybrid identity state by regulating NKX2-1 chromatin binding in LUAD. These findings nominate HNF4α as a driver of LUAD plasticity and a potential therapeutic target to overcome resistance.</jats:p>","journal":"Genes &amp; Development","year":2025,"id":660190,"datarank":0.20794415416798362,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"self_citation_contribution":0.20794415416798362,"citation_network_contribution":0.0,"self_endowment_contribution":0.20794415416798362,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":763264,"name":"Alena Yermalovich","orcid":"0000-0003-4029-2688","position":1,"is_corresponding":false},{"id":107871,"name":"Matthew Meyerson","orcid":"0000-0002-9133-8108","position":2,"is_corresponding":false},{"id":1171123,"name":"Alice Feng","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Lineage rewiring in lung adenocarcinoma via HNF4α and NKX2-1 dynamics","abstract":"<jats:p>Lineage plasticity drives treatment resistance in lung adenocarcinoma (LUAD) as cancer cells adopt new identities. 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