1. Epithelial-mesenchymal transition sensitizes breast cancer cells to cell death via the fungus-derived sesterterpenoid ophiobolin A.
- Author
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Reisenauer, Keighley N., Tao, Yongfeng, Das, Provas, Song, Shuxuan, Svatek, Haleigh, Patel, Saawan D., Mikhail, Sheridan, Ingros, Alec, Sheesley, Peter, Masi, Marco, Boari, Angela, Evidente, Antonio, Kornienko, Alexander, Romo, Daniel, and Taube, Joseph
- Subjects
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EPITHELIAL-mesenchymal transition , *BREAST cancer treatment , *CANCER chemotherapy , *CELL death , *OPHIOBOLIN A , *DOXORUBICIN - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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