{"doi":"10.1038/s41598-021-89923-9","title":"Epithelial-mesenchymal transition sensitizes breast cancer cells to cell death via the fungus-derived sesterterpenoid ophiobolin A","abstract":"The epithelial-mesenchymal transition (EMT) imparts properties of cancer stem-like cells, including resistance to frequently used chemotherapies, necessitating the identification of molecules that induce cell death specifically in stem-like cells with EMT properties. Herein, we demonstrate that breast cancer cells enriched for EMT features are more sensitive to cytotoxicity induced by ophiobolin A (OpA), a sesterterpenoid natural product. Using a model of experimentally induced EMT in human mammary epithelial (HMLE) cells, we show that EMT is both necessary and sufficient for OpA sensitivity. Moreover prolonged, sub-cytotoxic exposure to OpA is sufficient to suppress EMT-imparted CSC features including sphere formation and resistance to doxorubicin. In vivo growth of CSC-rich mammary cell tumors, is suppressed by OpA treatment. These data identify a driver of EMT-driven cytotoxicity with significant potential for use either in combination with standard chemotherapy or for tumors enriched for EMT features.","journal":"Scientific Reports","year":2021,"id":177308,"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":20,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9559,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":620989,"name":"Yongfeng Tao","orcid":"0000-0001-8884-204X","position":1,"is_corresponding":false},{"id":721005,"name":"Provas Das","orcid":"0000-0002-4339-7445","position":2,"is_corresponding":false},{"id":721006,"name":"Shuxuan Song","orcid":"0000-0002-1635-7085","position":3,"is_corresponding":false},{"id":721548,"name":"Haleigh Svatek","orcid":null,"position":4,"is_corresponding":false},{"id":683154,"name":"Saawan D. Patel","orcid":"0000-0003-3185-7026","position":5,"is_corresponding":false},{"id":721549,"name":"Sheridan Mikhail","orcid":null,"position":6,"is_corresponding":false},{"id":721550,"name":"Alec Ingros","orcid":null,"position":7,"is_corresponding":false},{"id":721007,"name":"Peter Sheesley","orcid":"0000-0003-1116-680X","position":8,"is_corresponding":false},{"id":545869,"name":"Marco Masi","orcid":"0000-0003-0609-8902","position":9,"is_corresponding":false},{"id":721008,"name":"Angela Boari","orcid":"0000-0003-1444-019X","position":10,"is_corresponding":false},{"id":545867,"name":"Antonio Evidente","orcid":"0000-0001-9110-1656","position":11,"is_corresponding":false},{"id":526597,"name":"Alexander Kornienko","orcid":"0000-0003-2041-7367","position":12,"is_corresponding":false},{"id":342114,"name":"Daniel Romo","orcid":"0000-0003-3805-092X","position":13,"is_corresponding":false},{"id":721009,"name":"Joseph H. Taube","orcid":"0000-0002-3636-5189","position":14,"is_corresponding":false},{"id":721004,"name":"Keighley Reisenauer","orcid":"0000-0003-0067-5684","position":0,"is_corresponding":true}],"reference_count":73,"raw_metadata":null,"created_at":"2026-07-18T23:47:28.018172Z","pmid":"34017048","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":[]}