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

doi:10.1016/j.celrep.2014.12.032

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

Gastroenterology and Hepatology

Research output: Contribution to journal › Article › peer-review

93 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 language	English (US)
Pages (from-to)	131-139
Number of pages	9
Journal	Cell reports
Volume	10
Issue number	2
DOIs	https://doi.org/10.1016/j.celrep.2014.12.032
State	Published - Jan 13 2015

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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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

Schmidt, JM, Panzilius, E, Bartsch, HS, Irmler, M, Beckers, J, Kari, V, Linnemann, JR, Dragoi, D, Hirschi, B, Kloos, UJ, Sass, S, Theis, F, Kahlert, S, Johnsen, SA, Sotlar, K & Scheel, CH 2015, 'Stem-cell-like properties and epithelial plasticity arise as stable traits after transient twist1 activation', Cell reports, vol. 10, no. 2, pp. 131-139. https://doi.org/10.1016/j.celrep.2014.12.032

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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.",

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

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AU - Beckers, Johannes

AU - Kari, Vijayalakshmi

AU - Linnemann, Jelena R.

AU - Dragoi, Diana

AU - Hirschi, Benjamin

AU - Kloos, Uwe J.

AU - Sass, Steffen

AU - Theis, Fabian

AU - Kahlert, Steffen

AU - Johnsen, Steven A.

AU - Sotlar, Karl

AU - Scheel, Christina H.

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AB - 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.

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

Abstract

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