Epithelial-mesenchymal transition sensitizes breast cancer cells to cell death via the fungus-derived sesterterpenoid ophiobolin A
| Autor: | Saawan D. Patel, Shuxuan Song, Provas Das, Alec Ingros, Sheridan Mikhail, Haleigh Svatek, Angela Boari, Peter Sheesley, Antonio Evidente, Yongfeng Tao, Alexander Kornienko, Marco Masi, Daniel Romo, Joseph H. Taube, Keighley N. Reisenauer |
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| Přispěvatelé: | Reisenauer, Keighley N, Tao, Yongfeng, Das, Prova, Song, Shuxuan, Svatek, Haleigh, Patel, Saawan D, Mikhail, Sheridan, Ingros, Alec, Sheesley, Peter, Masi, Marco, Boari, Angela, Evidente, Antonio, Kornienko, Alexander, Romo, Daniel, Taube, Joseph |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
ophiobolin A
Programmed cell death natural product Cell biology Epithelial-Mesenchymal Transition Sesterterpenes Cancer therapy medicine.medical_treatment Science Breast Neoplasms Mice SCID Article Cancer stem cell In vivo Cell Line Tumor medicine Animals Humans Doxorubicin Epithelial–mesenchymal transition Cytotoxicity Drechslera Cancer Cell Proliferation Chemotherapy Multidisciplinary Cell Death Chemistry Cancer stem cells Twist-Related Protein 1 Fungi Nuclear Proteins Epithelial Cells medicine.disease Gene Expression Regulation Neoplastic MicroRNAs Aspergillus Phenotype embryonic structures Cancer research cytotoxicity Medicine Female medicine.drug |
| Zdroj: | Scientific Reports Scientific Reports, Vol 11, Iss 1, Pp 1-10 (2021) Scientific reports (Nature Publishing Group) 11 (2021). doi:10.1038/s41598-021-89923-9 info:cnr-pdr/source/autori:Reisenauer K.N.; Tao Y.; Das P.; Song S.; Svatek H.; Patel S.D.; Mikhail S.; Ingros A.; Sheesley P.; Masi M.; Boari A.; Evidente A.; Kornienko A.; Romo D.; Taube J./titolo:Epithelial-mesenchymal transition sensitizes breast cancer cells to cell death via the fungus-derived sesterterpenoid ophiobolin A/doi:10.1038%2Fs41598-021-89923-9/rivista:Scientific reports (Nature Publishing Group)/anno:2021/pagina_da:/pagina_a:/intervallo_pagine:/volume:11 |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-021-89923-9 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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