| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2042066 | Cell Reports | 2015 | 9 Pages |
•Transient Twist1 activation primes cells for stem-cell-like traits•Stable stem-cell-like traits arise after Twist1 deactivation•Transient, not continuous, Twist1 activity promotes invasive growth•Transient Twist1 elicits a stably altered plastic epithelial cell state
SummaryMaster 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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