title: Endoplasmic reticulum protein 29 regulates epithelial cell integrity during the mesenchymal-epithelial transition in breast cancer cells.
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.
authors.affiliation: Department of Pathology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: I F
authors.initials: IF
authors.lastname: Bambang
authors.forename: Y K
authors.initials: YK
authors.lastname: Lee
authors.forename: D R
authors.initials: DR
authors.lastname: Richardson
authors.forename: D
authors.initials: D
authors.lastname: Zhang
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D005260:Female; D055785:Gene Knockdown Techniques; D006360:Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D061986:MCF-7 Cells; D018613:Microscopy, Confocal; D010641:Phenotype; D014162:Transfection; D015854:Up-Regulation; D051176:beta Catenin / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism
chemical_list: C495270:CTNNB1 protein, human; D015820:Cadherins; C491738:ERP29 protein, human; D006360:Heat-Shock Proteins; D051176:beta Catenin