{"doi":"10.7554/elife.81288","title":"EHD2 overexpression promotes tumorigenesis and metastasis in triple-negative breast cancer by regulating store-operated calcium entry","abstract":"With nearly all cancer deaths a result of metastasis, elucidating novel pro-metastatic cellular adaptations could provide new therapeutic targets. Here, we show that overexpression of the EPS15-Homology Domain-containing 2 (EHD2) protein in a large subset of breast cancers (BCs), especially the triple-negative (TNBC) and HER2+ subtypes, correlates with shorter patient survival. The mRNAs for EHD2 and Caveolin-1/2, structural components of caveolae, show co-overexpression across breast tumors, predicting shorter survival in basal-like BC. EHD2 shRNA knockdown and CRISPR-Cas9 knockout with mouse Ehd2 rescue, in TNBC cell line models demonstrate a major positive role of EHD2 in promoting tumorigenesis and metastasis. Mechanistically, we link these roles of EHD2 to store-operated calcium entry (SOCE), with EHD2-dependent stabilization of plasma membrane caveolae ensuring high cell surface expression of the SOCE-linked calcium channel Orai1. The novel EHD2-SOCE oncogenic axis represents a potential therapeutic target in EHD2- and CAV1/2-overexpressing BC.","journal":"eLife","year":2023,"id":336782,"datarank":0.44166584687496613,"base_score":2.9444389791664403,"endowment":2.9444389791664403,"self_citation_contribution":0.44166584687496613,"citation_network_contribution":0.0,"self_endowment_contribution":0.44166584687496613,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":18,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9626,"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":415305,"name":"Timothy A. Bielecki","orcid":"0000-0003-4561-0892","position":1,"is_corresponding":false},{"id":415301,"name":"Bhopal Mohapatra","orcid":"0000-0003-3434-4306","position":2,"is_corresponding":false},{"id":416742,"name":"Namista Islam","orcid":null,"position":3,"is_corresponding":false},{"id":416739,"name":"Insha Mushtaq","orcid":null,"position":4,"is_corresponding":false},{"id":416740,"name":"Aaqib M. Bhat","orcid":null,"position":5,"is_corresponding":false},{"id":384736,"name":"Sameer Mirza","orcid":"0000-0002-9394-2421","position":6,"is_corresponding":false},{"id":415303,"name":"Sukanya Chakraborty","orcid":"0000-0003-1238-7962","position":7,"is_corresponding":false},{"id":736065,"name":"Mohsin Ali Raza","orcid":"0000-0002-3496-0283","position":8,"is_corresponding":false},{"id":415307,"name":"Matthew D. Storck","orcid":"0000-0002-4029-8943","position":9,"is_corresponding":false},{"id":581628,"name":"Michael S. Toss","orcid":"0000-0002-9077-3984","position":10,"is_corresponding":false},{"id":613529,"name":"Jane L. Meza","orcid":null,"position":11,"is_corresponding":false},{"id":719139,"name":"Wallace B. Thoreson","orcid":"0000-0001-7104-042X","position":12,"is_corresponding":false},{"id":312106,"name":"Donald W. Coulter","orcid":"0000-0002-7829-0971","position":13,"is_corresponding":false},{"id":320592,"name":"Emad A. Rakha","orcid":"0000-0002-5009-5525","position":14,"is_corresponding":false},{"id":562956,"name":"Vimla Band","orcid":"0000-0003-2014-7205","position":15,"is_corresponding":false},{"id":415311,"name":"Hamid Band","orcid":"0000-0002-4996-9002","position":16,"is_corresponding":false},{"id":415302,"name":"Haitao Luan","orcid":"0000-0002-9831-167X","position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:10:21.947540Z","pmid":"36625722","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":[]}