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

Johanna M Schmidt1, Elena Panzilius1, Harald S Bartsch2

  • 1Institute of Stem Cell Research, Helmholtz Center for Health and Environmental Research Munich, 85764 Neuherberg, Germany.

Cell Reports
|January 13, 2015
PubMed

Insights

Transient activation of Twist1 (a key regulator in cancer) primes cells for stem-like properties. Deactivation of Twist1 allows these properties to emerge, promoting cancer cell invasion and metastasis.

Area of Science:

  • Cancer biology
  • Cellular plasticity
  • Metastasis research

Background:

  • Master regulators like Twist1 and Snail1 are linked to cancer invasiveness and stem cell generation.
  • Persistent activity of these regulators can paradoxically inhibit stem-cell-like properties and metastatic outgrowth.

Purpose of the Study:

  • To investigate the role of Twist1 dynamics in cancer stem cell properties and metastasis.
  • To elucidate the mechanism by which transient Twist1 activation facilitates the entire metastatic cascade.

Main Methods:

  • Analysis of Twist1 activation and deactivation in mammary epithelial cells.
  • Assessment of stem-cell-like properties and gene expression profiles.
  • Evaluation of invasive growth behavior post-mesenchymal-epithelial transition (MET).

Main Results:

  • Twist1 activation primes mammary epithelial cells for stem-cell properties, which manifest upon Twist1 deactivation.
  • Cells undergoing mesenchymal-epithelial transition (MET) do not revert to their original state, exhibiting invasive growth.
  • A distinct gene expression profile is observed in cells post-MET.

Conclusions:

  • Transient Twist1 activation is crucial for initiating stem-cell-like properties and promoting metastasis.
  • The mesenchymal-epithelial transition (MET) following transient Twist1 activation leads to a stable, invasive phenotype.
  • This mechanism explains how transient master regulator activity drives invasion, dissemination, and metastatic outgrowth.

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