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.

Epithelial-mesenchymal transition sensitizes breast cancer cells to cell death via the fungus-derived sesterterpenoid ophiobolin A / 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; Taube, Joseph. - In: SCIENTIFIC REPORTS. - ISSN 2045-2322. - 11:1(2021), p. 10652. [10.1038/s41598-021-89923-9]

Epithelial-mesenchymal transition sensitizes breast cancer cells to cell death via the fungus-derived sesterterpenoid ophiobolin A

Masi, Marco
Membro del Collaboration Group
;
2021

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.
2021
Epithelial-mesenchymal transition sensitizes breast cancer cells to cell death via the fungus-derived sesterterpenoid ophiobolin A / 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; Taube, Joseph. - In: SCIENTIFIC REPORTS. - ISSN 2045-2322. - 11:1(2021), p. 10652. [10.1038/s41598-021-89923-9]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/904347
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