PuSH - Publikationsserver des Helmholtz Zentrums München: Stem-cell-like properties and epithelial plasticity arise as stable traits after transient Twist1 activation.

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Schmidt, J. ; Panzilius, E. ; Bartsch, H.S.* ; Irmler, M. ; Beckers, J. ; Kari, V.* ; Linnemann, J. ; Dragoi, D. ; Hirschi, B. ; Kloos, U. ; Sass, S. ; Theis, F.J. ; Kahlert, S.* ; Johnsen, S.A.* ; Sotlar, K.* ; Scheel, C.

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

Cell Rep. 10, 131-139 (2015)

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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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