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. 2015 Jan 13;10(2):131-9.
doi: 10.1016/j.celrep.2014.12.032. Epub 2015 Jan 8.

Stem-cell-like properties and epithelial plasticity arise as stable traits after transient Twist1 activation

Johanna M Schmidt  1 , Elena Panzilius  1 , Harald S Bartsch  2 , Martin Irmler  3 , Johannes Beckers  4 , Vijayalakshmi Kari  5 , Jelena R Linnemann  1 , Diana Dragoi  1 , Benjamin Hirschi  1 , Uwe J Kloos  1 , Steffen Sass  6 , Fabian Theis  7 , Steffen Kahlert  8 , Steven A Johnsen  5 , Karl Sotlar  2 , Christina H Scheel  9
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Free article

Stem-cell-like properties and epithelial plasticity arise as stable traits after transient Twist1 activation

Johanna M Schmidt et al. Cell Rep. .
Free article

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.

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