{"doi":"10.3390/cancers15061866","title":"Non-Oncogene Addiction of KRAS-Mutant Cancers to IL-1β via Versican and Mononuclear IKKβ","abstract":"Kirsten rat sarcoma virus (KRAS)-mutant cancers are frequent, metastatic, lethal, and largely undruggable. While interleukin (IL)-1β and nuclear factor (NF)-κB inhibition hold promise against cancer, untargeted treatments are not effective. Here, we show that human KRAS-mutant cancers are addicted to IL-1β via inflammatory versican signaling to macrophage inhibitor of NF-κB kinase (IKK) β. Human pan-cancer and experimental NF-κB reporter, transcriptome, and proteome screens reveal that KRAS-mutant tumors trigger macrophage IKKβ activation and IL-1β release via secretory versican. Tumor-specific versican silencing and macrophage-restricted IKKβ deletion prevents myeloid NF-κB activation and metastasis. Versican and IKKβ are mutually addicted and/or overexpressed in human cancers and possess diagnostic and prognostic power. Non-oncogene KRAS/IL-1β addiction is abolished by IL-1β and TLR1/2 inhibition, indicating cardinal and actionable roles for versican and IKKβ in metastasis.","journal":"Cancers","year":2023,"id":365330,"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":6,"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":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1120834,"name":"Giannoula Ntaliarda","orcid":"0000-0002-2299-6027","position":1,"is_corresponding":false},{"id":1120835,"name":"Georgios Skiadas","orcid":"0000-0002-7377-8783","position":2,"is_corresponding":false},{"id":1120836,"name":"Anne‐Sophie Lamort","orcid":"0000-0001-5495-9995","position":3,"is_corresponding":false},{"id":1120837,"name":"Malamati Vreka","orcid":"0000-0002-2625-5832","position":4,"is_corresponding":false},{"id":1115375,"name":"Antonia Marazioti","orcid":"0000-0002-1978-1121","position":5,"is_corresponding":false},{"id":1120838,"name":"Ioannis Lilis","orcid":"0000-0002-0483-4120","position":6,"is_corresponding":false},{"id":1121228,"name":"Eleni Bouloukou","orcid":null,"position":7,"is_corresponding":false},{"id":1120839,"name":"Georgia A. Giotopoulou","orcid":"0000-0001-5621-6802","position":8,"is_corresponding":false},{"id":1120840,"name":"Mario Pepe","orcid":"0000-0002-1485-9022","position":9,"is_corresponding":false},{"id":1120841,"name":"Stefanie Weiß","orcid":"0000-0002-4059-7417","position":10,"is_corresponding":false},{"id":1120842,"name":"Agnese Petrera","orcid":"0000-0002-0583-6195","position":11,"is_corresponding":false},{"id":25246,"name":"Stefanie M. Hauck","orcid":"0000-0002-1630-6827","position":12,"is_corresponding":false},{"id":4828,"name":"Ina Koch","orcid":"0000-0002-8766-017X","position":13,"is_corresponding":false},{"id":553,"name":"Michael Lindner","orcid":"0000-0002-2106-0286","position":14,"is_corresponding":false},{"id":1121229,"name":"Rudolph Hatz","orcid":null,"position":15,"is_corresponding":false},{"id":1121230,"name":"J Behr","orcid":null,"position":16,"is_corresponding":false},{"id":1120843,"name":"Kristina A. M. Arendt","orcid":"0000-0002-4427-9379","position":17,"is_corresponding":false},{"id":1120844,"name":"Ioanna Giopanou","orcid":"0000-0003-4393-7517","position":18,"is_corresponding":false},{"id":1121231,"name":"David Brunn","orcid":null,"position":19,"is_corresponding":false},{"id":89034,"name":"Rajkumar Savai","orcid":"0000-0003-1538-2091","position":20,"is_corresponding":false},{"id":969219,"name":"Dieter E. Jenne","orcid":"0000-0002-1125-9144","position":21,"is_corresponding":false},{"id":1120845,"name":"Maarten de Château","orcid":"0009-0000-2351-0554","position":22,"is_corresponding":false},{"id":430234,"name":"Fiona E. Yull","orcid":"0000-0003-1636-7942","position":23,"is_corresponding":false},{"id":264692,"name":"Timothy S. Blackwell","orcid":"0000-0002-0337-7052","position":24,"is_corresponding":false},{"id":1115376,"name":"Georgios T. Stathopoulos","orcid":"0000-0002-9215-6461","position":25,"is_corresponding":false},{"id":1120833,"name":"Μάγδα Σπέλλα","orcid":"0000-0003-2505-7778","position":0,"is_corresponding":true}],"reference_count":62,"raw_metadata":null,"created_at":"2026-07-19T01:14:46.760245Z","pmid":"36980752","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":[]}