Stem-Cell-like Properties and Epithelial Plasticity Arise as Stable Traits after Transient Twist1 Activation
2015 | journal article. A publication with affiliation to the University of Göttingen.
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Stem-Cell-like Properties and Epithelial Plasticity Arise as Stable Traits after Transient Twist1 Activation
Schmidt, J. M.; Panzilius, E.; Bartsch, H. S.; Irmler, M.; Beckers, J.; Kari, V. & Linnemann, J. R. et al. (2015)
Cell Reports, 10(2) pp. 131-139. DOI: https://doi.org/10.1016/j.celrep.2014.12.032
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Details
- Authors
- Schmidt, Johanna M.; Panzilius, Elena; Bartsch, Harald S.; Irmler, Martin; Beckers, Johannes; Kari, Vijayalakshmi; Linnemann, Jelena R.; Dragoi, Diana; Hirschi, Benjamin; Kloos, Uwe J.; Sass, Steffen; Theis, Fabian J.; Kahlert, Steffen; Johnsen, Steven A.; Sotlar, Karl; Scheel, Christina H.
- 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 inhibits stem-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 of the metastatic cascade; i.e., invasion, dissemination, and metastatic outgrowth at distant sites.
- Issue Date
- 2015
- Status
- published
- Publisher
- Cell Press
- Journal
- Cell Reports
- ISSN
- 2211-1247
- Sponsor
- German Cancer Aid Foundation [110225, 111600]