{"doi":"10.1016/j.celrep.2025.116185","title":"Mutant RIT1 cooperates with YAP to drive an EMT-like lung cancer state","abstract":"Mutations in \"Ras-like in all tissues\" ( RIT1 ) occur in up to 2% of lung adenocarcinomas and are mutually exclusive with KRAS and EGFR mutations, suggesting that RIT1 may act as a non-canonical driver oncogene in lung cancer. However, the lack of a RIT1 -mutant lung cancer model has hindered the development and testing of RIT1-targeted therapeutics. Here, we report a mouse model with conditional regulation of the cancer-associated RIT1 M90I variant. We show that autochthonous expression of RIT1 M90I and combined inactivation of Nf2 and p53 drives an aggressive lung cancer with 100% penetrance and short latency. Oncogenic cooperation between RIT1 M90I and p53/Nf2 loss is driven by synergistic activation of AP-1 transcription factors and can be reversed by the combined inhibition of MEK and TEAD. These data identify YAP/TEAD as a mediator of RIT1's oncogenic capability and nominate TEAD as a potential drug target in RIT1 -mutant lung cancer.","journal":"Cell Reports","year":2025,"id":554224,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9549,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1144574,"name":"Siobhan O’Brien","orcid":"0000-0003-4958-1080","position":1,"is_corresponding":false},{"id":454749,"name":"Saksham Gupta","orcid":"0000-0002-7538-6345","position":2,"is_corresponding":false},{"id":580573,"name":"Sitapriya Moorthi","orcid":"0000-0001-6372-5170","position":3,"is_corresponding":false},{"id":84953,"name":"Maria McSharry","orcid":"0000-0001-5962-5441","position":4,"is_corresponding":false},{"id":563576,"name":"Shriya Kamlapurkar","orcid":"0000-0002-2686-3387","position":5,"is_corresponding":false},{"id":1357331,"name":"Amy R. Lowe","orcid":null,"position":6,"is_corresponding":false},{"id":1068202,"name":"Annie Waldum","orcid":null,"position":7,"is_corresponding":false},{"id":84952,"name":"April Lo","orcid":"0000-0001-6128-9846","position":8,"is_corresponding":false},{"id":575469,"name":"Fujiko Duke","orcid":null,"position":9,"is_corresponding":false},{"id":21506,"name":"Feinan Wu","orcid":"0000-0002-4962-1874","position":10,"is_corresponding":false},{"id":650054,"name":"Mark B. Headley","orcid":"0000-0002-0924-9326","position":11,"is_corresponding":false},{"id":1109204,"name":"Elizabeth Cromwell","orcid":"0000-0003-1636-6691","position":12,"is_corresponding":false},{"id":956639,"name":"Raisa Glabman","orcid":"0000-0003-1492-8830","position":13,"is_corresponding":false},{"id":364431,"name":"Amanda Koehne","orcid":"0000-0002-1397-6964","position":14,"is_corresponding":false},{"id":1357029,"name":"Marga B. Rominger","orcid":"0000-0003-2553-1687","position":0,"is_corresponding":true}],"reference_count":75,"raw_metadata":null,"created_at":"2026-07-19T02:54:50.112989Z","pmid":"41004338","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":[]}