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TGF-β-mediated Endothelial to Mesenchymal Transition (EndMT) and the Functional Assessment of EndMT Effectors using CRISPR/Cas9 Gene Editing
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Snail destabilizes cell surface Crumbs3a.

Jennifer L Harder1, Eileen L Whiteman, Jay N Pieczynski

  • 1Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.

Traffic (Copenhagen, Denmark)
|May 5, 2012
PubMed
Summary
This summary is machine-generated.

Snail protein destabilizes Crumbs3a through post-translational modification, accelerating epithelial to mesenchymal transition (EMT). This post-translational regulation complements Snail

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • Epithelial to mesenchymal transition (EMT) involves loss of cell polarity.
  • Crumbs3a is crucial for epithelial apical membrane and tight junction formation.
  • Snail is a key inducer of EMT and a transcriptional regulator of Crumbs3.

Purpose of the Study:

  • To investigate the non-transcriptional roles of Snail in EMT.
  • To determine if Snail affects Crumbs3a stability and how.
  • To elucidate the post-translational regulation of Crumbs3a by Snail.

Main Methods:

  • SNAP-tag labeling was used to track cell surface Crumbs3a.
  • Cell surface half-life of Crumbs3a was measured under EMT conditions.
  • Glycosylation patterns of Crumbs3a, specifically sialylation, were analyzed.

Main Results:

  • Cell surface Crumbs3a has a half-life of approximately 3 hours.
  • Snail induction of EMT significantly reduces Crumbs3a cell surface half-life.
  • Snail promotes differential glycosylation, including sialylation, of Crumbs3a.

Conclusions:

  • Crumbs3a is a post-translational target of Snail, in addition to being a transcriptional target.
  • Snail-induced post-translational modification and destabilization of Crumbs3a enhance EMT.
  • This dual regulation by Snail contributes to the loss of epithelial polarity during EMT.