{"doi":"10.1093/neuonc/noae182","title":"EGFR and EGFRvIII coopt host defense pathways promoting progression in glioblastoma","abstract":"BACKGROUND: Co-amplification of the epidermal growth factor receptor (EGFR) and EGFRvIII, a tumor-specific truncation mutant of EGFR, represent hallmark genetic lesions in glioblastoma. METHODS: We used phospho-proteomics, RNA-sequencing, TCGA data, glioblastoma cell culture, and mouse models to study the signal transduction mediated by EGFR and EGFRvIII. RESULTS: We report that EGFR and EGFRvIII stimulate the innate immune defense receptor Toll-like Receptor 2 (TLR2); and that knockout of TLR2 dramatically improved survival in orthotopic glioblastoma xenografts. EGFR and EGFRvIII activated TLR2 in a ligand-independent manner, promoting tumor growth and immune evasion. We show that EGFR and EGFRvIII cooperate to activate the Rho-associated protein kinase ROCK2, which modulated malignant progression both by activating TLR2 and WNT signaling, and through remodeling the tumor microenvironment. CONCLUSIONS: Together, our findings show that EGFR and EGFRvIII cooperate to drive tumor progression through ROCK2 and downstream WNT-β-catenin/TLR2 signaling pathways.","journal":"Neuro-Oncology","year":2024,"id":437220,"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":11,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9546,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":558480,"name":"Qi-Wen Fan","orcid":null,"position":1,"is_corresponding":false},{"id":1167571,"name":"Linyu Wang","orcid":"0000-0002-5455-3503","position":2,"is_corresponding":false},{"id":969264,"name":"Hiroyuki Yoda","orcid":"0000-0002-5528-8940","position":3,"is_corresponding":false},{"id":1226851,"name":"Megumi J. Barata","orcid":null,"position":4,"is_corresponding":false},{"id":342867,"name":"David Jimenez‐Morales","orcid":"0000-0003-4356-6461","position":5,"is_corresponding":false},{"id":87614,"name":"Joanna J. Phillips","orcid":"0000-0002-3789-8120","position":6,"is_corresponding":false},{"id":1356,"name":"Danielle L. Swaney","orcid":"0000-0001-6119-6084","position":7,"is_corresponding":false},{"id":2366,"name":"Erica Stevenson","orcid":"0000-0001-7853-1854","position":8,"is_corresponding":false},{"id":241280,"name":"Ethan Lee","orcid":"0000-0001-8405-6156","position":9,"is_corresponding":false},{"id":1363,"name":"Nevan J. Krogan","orcid":"0000-0003-4902-337X","position":10,"is_corresponding":false},{"id":351797,"name":"William A. Weiss","orcid":"0000-0003-2230-9132","position":11,"is_corresponding":false},{"id":976127,"name":"Zhenyi An","orcid":null,"position":0,"is_corresponding":true}],"reference_count":50,"raw_metadata":null,"created_at":"2026-07-19T02:00:29.872940Z","pmid":"39248287","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":[]}