Stem-Cell-like Properties and Epithelial Plasticity Arise as Stable Traits after Transient Twist1 Activation
| Autor: | Steven A. Johnsen, Benjamin Hirschi, Harald Bartsch, Martin Irmler, Steffen Sass, Johanna M. Schmidt, Elena Panzilius, Fabian J. Theis, D Dragoi, Steffen Kahlert, Karl Sotlar, Christina Scheel, Johannes Beckers, Uwe J. Kloos, Jelena R. Linnemann, Vijayalakshmi Kari |
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| Rok vydání: | 2015 |
| Předmět: |
Epithelial-Mesenchymal Transition
animal structures Antineoplastic Agents Hormonal Cell Culture Techniques Breast Neoplasms Biology General Biochemistry Genetics and Molecular Biology Cell Line Cell Movement Cancer stem cell Gene expression medicine Humans lcsh:QH301-705.5 Cell Proliferation Metastatic cascade Transition (genetics) Stem Cells Twist-Related Protein 1 Nuclear Proteins Epithelial Cells Epithelium ddc Cell biology Tamoxifen medicine.anatomical_structure lcsh:Biology (General) Immunology Epithelial plasticity Female Snail Family Transcription Factors Stem cell Disseminated cancer Transcription Factors |
| Zdroj: | Cell Reports, Vol 10, Iss 2, Pp 131-139 (2015) Cell Rep. 10, 131-139 (2015) |
| ISSN: | 2211-1247 |
| DOI: | 10.1016/j.celrep.2014.12.032 |
| Popis: | 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 inhibitsstem-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 ofthe metastatic cascade; i.e., invasion, dissemination, and metastatic outgrowth at distant sites. |
| Databáze: | OpenAIRE |
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