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Updated: May 22, 2026

Induction and Analysis of Epithelial to Mesenchymal Transition
Published on: August 27, 2013
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.
Abstract:
The epithelial-mesenchymal transition (EMT) correlates with disruption of cell-cell adhesion, loss of cell polarity and development of epithelial cell malignancy. Identifying novel molecules that inhibit EMT has profound potential for developing mechanism-based therapeutics. We previously demonstrated that the endoplasmic reticulum protein 29 (ERp29) is a novel factor that can drive mesenchymal-epithelial transition (MET) and induce cell growth arrest in MDA-MB-231 cells. Here, we show that ERp29 is an important molecule in establishing epithelial cell integrity during the MET. We demonstrate that ERp29 regulates MET in a cell context-dependent manner. ERp29 overexpression induced a complete MET in mesenchymal MDA-MB-231 cells through downregulating the expression of transcriptional repressors (for example, Slug, Snai1, ZEB2 and Twist) of E-cadherin. In contrast, overexpression of ERp29 induces incomplete MET in basal-like BT549 cells in which the expression of EMT-related markers (for example, vimentin; cytokeratin 19 (CK19) and E-cadherin) and the transcriptional repressors of E-cadherin were not altered. However, ERp29 overexpression in both cell-types resulted in loss of filamentous stress fibers, formation of cortical actin and restoration of an epithelial phenotype. Mechanistic studies revealed that overexpression of ERp29 in both cell-types upregulated the expression of TJ proteins (zonula-occludens-1 (ZO-1) and occludin) and the core apical-basal polarity proteins (Par3 and Scribble) at the membrane to enhance cell-cell contact and cell polarization. Knockdown of ERp29 in the epithelial MCF-7 cells decreased the expression of these proteins, leading to the disruption of cell-cell adhesion. Taken together, ERp29 is a novel molecule that regulates MET and epithelial cell integrity in breast cancer cells.
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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