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...
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2021
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oai:doaj.org-article:d75b28ec027d450f93ccf403759229802021-12-02T15:45:26ZEpithelial-mesenchymal transition sensitizes breast cancer cells to cell death via the fungus-derived sesterterpenoid ophiobolin A10.1038/s41598-021-89923-92045-2322https://doaj.org/article/d75b28ec027d450f93ccf403759229802021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-89923-9https://doaj.org/toc/2045-2322Abstract 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.Keighley N. ReisenauerYongfeng TaoProvas DasShuxuan SongHaleigh SvatekSaawan D. PatelSheridan MikhailAlec IngrosPeter SheesleyMarco MasiAngela BoariAntonio EvidenteAlexander KornienkoDaniel RomoJoseph TaubeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021) |
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Medicine R Science Q Keighley N. Reisenauer Yongfeng Tao Provas Das Shuxuan Song Haleigh Svatek Saawan D. Patel Sheridan Mikhail Alec Ingros Peter Sheesley Marco Masi Angela Boari Antonio Evidente Alexander Kornienko Daniel Romo Joseph Taube Epithelial-mesenchymal transition sensitizes breast cancer cells to cell death via the fungus-derived sesterterpenoid ophiobolin A |
| description |
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. |
| format |
article |
| author |
Keighley N. Reisenauer Yongfeng Tao Provas Das Shuxuan Song Haleigh Svatek Saawan D. Patel Sheridan Mikhail Alec Ingros Peter Sheesley Marco Masi Angela Boari Antonio Evidente Alexander Kornienko Daniel Romo Joseph Taube |
| author_facet |
Keighley N. Reisenauer Yongfeng Tao Provas Das Shuxuan Song Haleigh Svatek Saawan D. Patel Sheridan Mikhail Alec Ingros Peter Sheesley Marco Masi Angela Boari Antonio Evidente Alexander Kornienko Daniel Romo Joseph Taube |
| author_sort |
Keighley N. Reisenauer |
| title |
Epithelial-mesenchymal transition sensitizes breast cancer cells to cell death via the fungus-derived sesterterpenoid ophiobolin A |
| title_short |
Epithelial-mesenchymal transition sensitizes breast cancer cells to cell death via the fungus-derived sesterterpenoid ophiobolin A |
| title_full |
Epithelial-mesenchymal transition sensitizes breast cancer cells to cell death via the fungus-derived sesterterpenoid ophiobolin A |
| title_fullStr |
Epithelial-mesenchymal transition sensitizes breast cancer cells to cell death via the fungus-derived sesterterpenoid ophiobolin A |
| title_full_unstemmed |
Epithelial-mesenchymal transition sensitizes breast cancer cells to cell death via the fungus-derived sesterterpenoid ophiobolin A |
| title_sort |
epithelial-mesenchymal transition sensitizes breast cancer cells to cell death via the fungus-derived sesterterpenoid ophiobolin a |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/d75b28ec027d450f93ccf40375922980 |
| work_keys_str_mv |
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