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Induction and Analysis of Epithelial to Mesenchymal Transition
10:37

Induction and Analysis of Epithelial to Mesenchymal Transition

Published on: August 27, 2013

Dual regulation of Snail by GSK-3beta-mediated phosphorylation in control of epithelial-mesenchymal transition

Binhua P Zhou1, Jiong Deng, Weiya Xia

  • 1Department of Molecular and Cellular Oncology, Breast Cancer Basic Research Program, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.

Nature Cell Biology
|September 28, 2004
PubMed

Insights

The epithelial-mesenchymal transition (EMT) involves cancer cell motility. Glycogen synthase kinase 3 beta (GSK-3beta) regulates the Snail protein, a key factor in EMT, by controlling its stability and localization.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Biology

Background:

  • Epithelial-mesenchymal transition (EMT) is crucial for embryonic development and cancer progression.
  • Snail, a transcription factor, drives EMT by suppressing E-cadherin, but its regulatory mechanisms are unclear.

Purpose of the Study:

  • To elucidate the regulatory mechanisms governing Snail stability and function.
  • To investigate the role of GSK-3beta in Snail-mediated EMT.

Main Methods:

  • Protein stability assays to determine Snail half-life.
  • In vitro phosphorylation and ubiquitination assays.
  • Analysis of Snail subcellular localization and E-cadherin expression.
  • In vivo studies involving GSK-3beta inhibition.

Main Results:

  • Snail protein has a short half-life of approximately 25 minutes.
  • GSK-3beta phosphorylates Snail at two sites, impacting its ubiquitination and localization.
  • A non-phosphorylatable Snail variant (Snail-6SA) is hyper-stable and constitutively nuclear, promoting EMT.
  • GSK-3beta inhibition increases Snail levels and decreases E-cadherin expression in vivo.

Conclusions:

  • GSK-3beta acts as a critical regulator of Snail stability and function.
  • Snail and GSK-3beta form a molecular switch controlling EMT signaling pathways.
  • Targeting the Snail-GSK-3beta interaction may offer therapeutic strategies for cancers exhibiting EMT.

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