{"doi":"10.1002/jev2.12307","title":"An extracellular vesicular mutant KRAS‐associated protein complex promotes lung inflammation and tumor growth","abstract":"Extracellular vesicles (EVs) contain more than 100 proteins. Whether there are EVs proteins that act as an 'organiser' of protein networks to generate a new or different biological effect from that identified in EV-producing cells has never been demonstrated. Here, as a proof-of-concept, we demonstrate that EV-G12D-mutant KRAS serves as a leader that forms a protein complex and promotes lung inflammation and tumour growth via the Fn1/IL-17A/FGF21 axis. Mechanistically, in contrast to cytosol derived G12D-mutant KRAS complex from EVs-producing cells, EV-G12D-mutant KRAS interacts with a group of extracellular vesicular factors via fibronectin-1 (Fn1), which drives the activation of the IL-17A/FGF21 inflammation pathway in EV recipient cells. We show that: (i), depletion of EV-Fn1 leads to a reduction of a number of inflammatory cytokines including IL-17A; (ii) induction of IL-17A promotes lung inflammation, which in turn leads to IL-17A mediated induction of FGF21 in the lung; and (iii) EV-G12D-mutant KRAS complex mediated lung inflammation is abrogated in IL-17 receptor KO mice. These findings establish a new concept in EV function with potential implications for novel therapeutic interventions in EV-mediated disease processes.","journal":"Journal of Extracellular Vesicles","year":2023,"id":345643,"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":12,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9464,"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":295147,"name":"Yun Teng","orcid":"0000-0003-2365-1626","position":1,"is_corresponding":false},{"id":296756,"name":"Jingyao Mu","orcid":null,"position":2,"is_corresponding":false},{"id":295148,"name":"Fangyi Xu","orcid":"0000-0002-6764-8616","position":3,"is_corresponding":false},{"id":295150,"name":"Anil Kumar","orcid":"0000-0001-5242-1323","position":4,"is_corresponding":false},{"id":296757,"name":"Kumaran Sundaram","orcid":null,"position":5,"is_corresponding":false},{"id":1085608,"name":"Rajiv Malhotra","orcid":"0009-0008-6634-3387","position":6,"is_corresponding":false},{"id":1085609,"name":"Qingbo Xu","orcid":"0000-0003-2474-8155","position":7,"is_corresponding":false},{"id":381405,"name":"Joshua L. Hood","orcid":"0000-0003-3998-4118","position":8,"is_corresponding":false},{"id":1085610,"name":"Lifeng Zhang","orcid":"0000-0001-7394-5433","position":9,"is_corresponding":false},{"id":250194,"name":"Jun Yan","orcid":"0000-0003-2922-422X","position":10,"is_corresponding":false},{"id":339033,"name":"Michael L. Merchant","orcid":"0000-0003-4128-4057","position":11,"is_corresponding":false},{"id":284080,"name":"Juw Won Park","orcid":"0000-0002-4610-6893","position":12,"is_corresponding":false},{"id":250786,"name":"Gerald W. Dryden","orcid":"0000-0001-9787-4537","position":13,"is_corresponding":false},{"id":268445,"name":"Nejat K. Egilmez","orcid":"0000-0002-2544-2767","position":14,"is_corresponding":false},{"id":295156,"name":"Huang‐Ge Zhang","orcid":"0000-0001-9665-9202","position":15,"is_corresponding":false},{"id":295151,"name":"Mukesh K. Sriwastva","orcid":"0000-0003-4370-4625","position":0,"is_corresponding":true}],"reference_count":57,"raw_metadata":null,"created_at":"2026-07-19T01:11:44.152490Z","pmid":"36754903","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":[]}