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Updated: Apr 24, 2026

Induction and Analysis of Epithelial to Mesenchymal Transition
10:37

Induction and Analysis of Epithelial to Mesenchymal Transition

Published on: August 27, 2013

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PKD1 phosphorylation-dependent degradation of SNAIL by SCF-FBXO11 regulates epithelial-mesenchymal transition and

Hanqiu Zheng1, Minhong Shen2, Yin-Lian Zha3

  • 1Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.

Cancer Cell
|September 10, 2014
PubMed

Insights

Researchers found that the PKD1-FBXO11-SNAIL pathway regulates cancer metastasis. FBXO11 targets SNAIL for degradation, inhibiting epithelial-mesenchymal transition (EMT) and blocking tumor spread in breast cancer models.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cellular Biology

Background:

  • Metastatic dissemination is driven by epithelial-mesenchymal transition (EMT).
  • The transcription factor SNAIL is crucial for EMT, invasion, metastasis, and stemness.
  • Understanding SNAIL's posttranslational regulation is key to targeting metastasis.

Purpose of the Study:

  • To identify E3 ligases regulating SNAIL.
  • To elucidate the mechanism of SNAIL degradation.
  • To investigate the role of the identified pathway in breast cancer metastasis.

Main Methods:

  • Genome-wide E3 ligase siRNA library screen using luciferase assay.
  • Analysis of SNAIL ubiquitylation and degradation.
  • Assessment of FBXO11's function in breast cancer models.

Main Results:

  • SCF-FBXO11 was identified as an E3 ligase targeting SNAIL for degradation.
  • SNAIL degradation by FBXO11 requires Ser-11 phosphorylation by protein kinase D1 (PKD1).
  • FBXO11 inhibits SNAIL-induced EMT, tumor initiation, and metastasis in breast cancer.

Conclusions:

  • The PKD1-FBXO11-SNAIL axis is a novel mechanism for posttranslational regulation of EMT.
  • This pathway represents a potential therapeutic target for inhibiting cancer metastasis.

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