Stem-cell-like properties and epithelial plasticity arise as stable traits after transient twist1 activation

Johanna M. Schmidt, Elena Panzilius, Harald S. Bartsch, Martin Irmler, Johannes Beckers, Vijayalakshmi Kari, Jelena R. Linnemann, Diana Dragoi, Benjamin Hirschi, Uwe J. Kloos, Steffen Sass, Fabian Theis, Steffen Kahlert, Steven A. Johnsen, Karl Sotlar, Christina H. Scheel

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80 Scopus citations

Abstract

Master regulators of the epithelial-mesenchymal transition such as Twist1 and Snail1 have been implicated in invasiveness and the generation of cancer stem cells, but their persistent activity inhibitsstem-cell-like properties and the outgrowth of disseminated cancer cells into macroscopic metastases. Here, we show that Twist1 activation primes a subset of mammary epithelial cells for stem-cell-like properties, which only emerge and stably persist following Twist1 deactivation. Consequently, when cells undergo a mesenchymal-epithelial transition (MET), they do not return to their original epithelial cell state, evidenced by acquisition of invasive growth behavior and a distinct gene expression profile. These data provide an explanation for how transient Twist1 activation may promote all steps ofthe metastatic cascade; i.e., invasion, dissemination, and metastatic outgrowth at distant sites.

Original languageEnglish (US)
Pages (from-to)131-139
Number of pages9
JournalCell reports
Volume10
Issue number2
DOIs
StatePublished - Jan 13 2015

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Schmidt, J. M., Panzilius, E., Bartsch, H. S., Irmler, M., Beckers, J., Kari, V., Linnemann, J. R., Dragoi, D., Hirschi, B., Kloos, U. J., Sass, S., Theis, F., Kahlert, S., Johnsen, S. A., Sotlar, K., & Scheel, C. H. (2015). Stem-cell-like properties and epithelial plasticity arise as stable traits after transient twist1 activation. Cell reports, 10(2), 131-139. https://doi.org/10.1016/j.celrep.2014.12.032