{"doi":"10.1242/jcs.264350","title":"Epidermal growth factor receptor is an essential component in E-cadherin force transduction complexes","abstract":"We present evidence that the association of the epithelial (E)-cadherin (CHD1) extracellular domain and epidermal growth factor receptor (EGFR, ErbB1) is obligatory for cadherin force transduction signaling. E-cadherin and EGFR associate at cell surfaces, independent of their cytoplasmic domains, and tension on E-cadherin activates EGFR signaling. Using engineered E-cadherin mutants that disrupt co-immunoprecipitation with EGFR, but not adhesion, we show that the hetero-receptor complex is required to mechanically activate signaling and downstream cytoskeletal remodeling at cadherin adhesions. The mutants localized the essential region on E-cadherin to domain 4 of the extracellular region (EC4). The ectodomain is also required for hetero-receptor colocalization at intercellular junctions. Although the E-cadherin mutants disrupt EGFR signaling, integrin pre-activation together with tension rescues cytoskeletal reinforcement at cadherin adhesions, confirming the role of integrins in intercellular force transduction. Furthermore, although E-cadherin suppresses EGFR-mediated proliferation, in response to extracellular matrix stiffening, the force-sensitive hetero-receptor complex regulates growth factor-dependent epithelial proliferation. These findings support the hypothesis that E-cadherin complexes with EGFR are mechano-switches at cell-cell contacts that directly couple intercellular force fluctuations to mitogen-dependent signaling.","journal":"Journal of Cell Science","year":2025,"id":546680,"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":0.9642,"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":1439185,"name":"Nicolas Allen","orcid":null,"position":1,"is_corresponding":false},{"id":1439186,"name":"Emaan Rauf","orcid":null,"position":2,"is_corresponding":false},{"id":382699,"name":"Deborah Leckband","orcid":"0000-0002-7557-766X","position":3,"is_corresponding":false},{"id":1438774,"name":"Yubo Zou","orcid":"0009-0009-7999-8486","position":0,"is_corresponding":true}],"reference_count":99,"raw_metadata":null,"created_at":"2026-07-19T02:53:36.567932Z","pmid":"40908853","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":[]}