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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; Kahlert, Steffen; Johnsen, Steven A.; Sotlar, Karl; Scheel, Christina H. (2015): Stem-Cell-like Properties and Epithelial Plasticity Arise as Stable Traits after Transient Twist1 Activation. In: Cell Reports, Vol. 10, No. 2: pp. 131-139
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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 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.