{"doi":"10.1002/1878-0261.12686","title":"RETRACTED: Novel C‐terminal heat shock protein 90 inhibitors target breast cancer stem cells and block migration, self‐renewal, and epithelial–mesenchymal transition","abstract":"In patients with triple-negative breast cancer (TNBC), evidence suggests that tumor-initiating cells (TIC) have stem cell-like properties, leading to invasion and metastasis. HSP90 plays a critical role in the conformational maintenance of many client proteins in TIC development. Therefore, we hypothesize that the novel C-terminal HSP90 inhibitors KU711 and KU758 can target TIC and represent a promising strategy for overcoming metastasis. Human breast cancer cells (MDA-MB-468LN, MDA-MB-231) treated with the HSP90 inhibitors KU711, KU758, and 17-AAG showed a 50-80% decrease in TIC markers CD44 and aldehyde dehydrogenase (P < 0.01) as assessed by flow cytometry. A decrease in sphere formation, which was used to assess self-renewal, was observed after the treatment of TNBC cells starting at 2.5 µm KU711 and 0.31 µm KU758. KU compounds also blocked the invasion and migration of TNBC cells in a dose-dependent manner. The knockdown of HSP90 clients was observed without any change in prosurvival HSP70 levels. In vivo, in a murine orthotopic breast cancer model, treatment with KU758 and KU711 yielded an approximately twofold and a fourfold reduction in tumor volumes versus control, respectively, without demonstrated toxicity. In conclusion, C-terminal HSP90 inhibitors are potent novel therapeutics against TNBC in vitro and in vivo as they target TICs and block invasion, EMT transition, and self-renewal.","journal":"Molecular Oncology","year":2020,"id":77271,"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":19,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9575,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":403535,"name":"Patrick T. Grogan","orcid":null,"position":1,"is_corresponding":false},{"id":282428,"name":"Ton Wang","orcid":"0000-0003-0437-3771","position":2,"is_corresponding":false},{"id":350060,"name":"Joseph Bazzill","orcid":"0000-0001-9779-6524","position":3,"is_corresponding":false},{"id":402501,"name":"Ang Zuo","orcid":"0000-0002-4075-8786","position":4,"is_corresponding":false},{"id":402502,"name":"Peter White","orcid":"0000-0003-2933-8323","position":5,"is_corresponding":false},{"id":403536,"name":"Avinaash Kalidindi","orcid":null,"position":6,"is_corresponding":false},{"id":402503,"name":"Dawn Kuszynski","orcid":"0000-0002-3182-8551","position":7,"is_corresponding":false},{"id":402504,"name":"Grace Wang","orcid":"0000-0003-2063-031X","position":8,"is_corresponding":false},{"id":288121,"name":"Brian S. J. Blagg","orcid":"0000-0002-6200-3480","position":9,"is_corresponding":false},{"id":402505,"name":"Mark S. Cohen","orcid":"0000-0002-2517-0757","position":10,"is_corresponding":false},{"id":402500,"name":"Chitra Subramanian","orcid":"0000-0003-1871-2834","position":0,"is_corresponding":true}],"reference_count":25,"raw_metadata":null,"created_at":"2026-07-18T21:48:50.085103Z","pmid":"32255264","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":[]}