Plate IV.519 · Publications
Stem-Cell-like Properties and Epithelial Plasticity Arise as Stable Traits after Transient Twist1 Activation
Article in Cell Reports, January 2015.
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.
Cite
@article{schmidt2015stem,
title = {{Stem-Cell-like Properties and Epithelial Plasticity Arise as Stable Traits after Transient Twist1 Activation}},
author = {Schmidt, Johanna M. and Panzilius, Elena and Bartsch, Harald S. and Irmler, Martin and Beckers, Johannes and Kari, Vijayalakshmi and Linnemann, Jelena R. and Dragoi, Diana and Hirschi, Benjamin and Kloos, Uwe J. and Sass, Steffen and Theis, Fabian and Kahlert, Steffen and Johnsen, Steven A. and Sotlar, Karl and Scheel, Christina H.},
journal = {Cell Reports},
publisher = {Elsevier BV},
year = {2015},
month = jan,
doi = {10.1016/j.celrep.2014.12.032},
url = {https://doi.org/10.1016/j.celrep.2014.12.032},
pmid = {25578726}
}