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


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Article Info

DATE

2021-05-20

AUTHORS

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

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. More... »

PAGES

10652

References to SciGraph publications

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41598-021-89923-9

    DOI

    http://dx.doi.org/10.1038/s41598-021-89923-9

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1138201456

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/34017048


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