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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

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MCRIP1, an ERK substrate, mediates ERK-induced gene silencing during epithelial-mesenchymal transition by regulating

Kenji Ichikawa1, Yuji Kubota2, Takanori Nakamura2

  • 1Division of Cell Signaling and Molecular Medicine, Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108-8639, Japan; Department of Cell Signaling and Molecular Medicine, Research Institute of Environmental Medicine, Nagoya University, Chikusa-ku, Nagoya 464-8601, Japan; Division of Molecular Cell Signaling, Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108-8639, Japan; Department of Biophysics and Biochemistry, Graduate School of Science, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.

Molecular Cell
|March 3, 2015
PubMed

Insights

The ERK pathway uses MCRIP1 to silence the E-cadherin gene during epithelial-mesenchymal transition (EMT). This mechanism, involving CtBP and ZEB1, is crucial for understanding cancer development.

Area of Science:

  • Molecular Biology
  • Epigenetics
  • Cancer Biology

Background:

  • The ERK pathway regulates gene expression, including tumor-suppressive genes like E-cadherin.
  • Epithelial-mesenchymal transition (EMT) involves E-cadherin repression, a process linked to cancer progression.
  • CtBP acts as a transcriptional co-repressor, but its link to ERK signaling in E-cadherin silencing was unclear.

Purpose of the Study:

  • To elucidate the functional relationship between ERK signaling and CtBP in E-cadherin gene silencing.
  • To identify key molecular players mediating ERK's effect on E-cadherin during EMT.

Main Methods:

  • Identification of ERK substrates.
  • Co-immunoprecipitation assays to study protein interactions.
  • Analysis of protein phosphorylation and its effect on DNA binding.

Main Results:

  • MCRIP1 was identified as an ERK substrate that links ERK signaling to CtBP.
  • MCRIP1 competitively inhibits the interaction between CtBP and ZEB1.
  • ERK-mediated phosphorylation of MCRIP1 releases CtBP, facilitating CtBP-ZEB1 complex formation and E-cadherin promoter silencing.

Conclusions:

  • A novel molecular mechanism reveals how ERK signaling induces epigenetic silencing of E-cadherin via MCRIP1 and CtBP during EMT.
  • This pathway's dysregulation contributes to cancer development.

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