Endoplasmic reticulum protein 29 regulates epithelial cell integrity during the mesenchymal-epithelial transition in

I F Bambang1, Y K Lee, D R Richardson

  • 1Department of Pathology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

Oncogene
|May 1, 2012
PubMed

Insights

Endoplasmic reticulum protein 29 (ERp29) drives mesenchymal-epithelial transition (MET) and restores epithelial cell integrity in breast cancer. ERp29 regulates MET differently based on cell type, impacting cell adhesion and polarity.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • The epithelial-mesenchymal transition (EMT) is linked to cancer malignancy.
  • Identifying molecules that inhibit EMT is crucial for therapeutic development.
  • Endoplasmic reticulum protein 29 (ERp29) was previously shown to induce mesenchymal-epithelial transition (MET) and cell growth arrest.

Purpose of the Study:

  • To investigate the role of ERp29 in establishing epithelial cell integrity during MET.
  • To determine the cell context-dependent regulation of MET by ERp29.
  • To elucidate the molecular mechanisms by which ERp29 influences epithelial phenotypes.

Main Methods:

  • Overexpression of ERp29 in mesenchymal (MDA-MB-231) and basal-like (BT549) breast cancer cells.
  • Analysis of EMT-related markers, including E-cadherin repressors and mesenchymal markers.
  • Assessment of actin cytoskeleton organization, tight junction (TJ) proteins, and apical-basal polarity proteins.

Main Results:

  • ERp29 overexpression induced complete MET in MDA-MB-231 cells by downregulating E-cadherin repressors.
  • ERp29 overexpression induced incomplete MET in BT549 cells without altering EMT markers.
  • In both cell types, ERp29 overexpression restored epithelial phenotype by reorganizing actin and enhancing cell-cell adhesion and polarity through TJ and polarity proteins.

Conclusions:

  • ERp29 is a novel regulator of MET and epithelial cell integrity in breast cancer.
  • ERp29's effect on MET is cell context-dependent.
  • ERp29 enhances epithelial characteristics by modulating cell adhesion and polarity proteins.

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