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Cell Rep. 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.

Author information

1
Institute of Stem Cell Research, Helmholtz Center for Health and Environmental Research Munich, 85764 Neuherberg, Germany.
2
Institute of Pathology, Medical School, Ludwig Maximilian University, 80337 Munich, Germany.
3
Institute of Experimental Genetics, Helmholtz Center Munich, 85764 Neuherberg, Germany.
4
Institute of Experimental Genetics, Helmholtz Center Munich, 85764 Neuherberg, Germany; Department of Experimental Genetics, Technical University Munich, 85354 Freising, Germany.
5
Department of General, Visceral and Pediatric Surgery, University Medical Center, 37075 Göttingen, Germany.
6
Institute of Computational Biology, Helmholtz Center Munich, 85764 Neuherberg, Germany.
7
Institute of Computational Biology, Helmholtz Center Munich, 85764 Neuherberg, Germany; Department of Mathematics, Technical University Munich, 85747 Garching, Germany.
8
Department of Obstetrics and Gynecology, Medical School, Ludwig Maximilian University, 80337 Munich, Germany.
9
Institute of Stem Cell Research, Helmholtz Center for Health and Environmental Research Munich, 85764 Neuherberg, Germany. Electronic address: christina.scheel@helmholtz-muenchen.de.

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.

PMID:
25578726
DOI:
10.1016/j.celrep.2014.12.032
[Indexed for MEDLINE]
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