Calreticulin represses E-cadherin gene expression in Madin-Darby canine kidney cells via Slug.
J Biol Chem
; 281(43): 32469-84, 2006 Oct 27.
Article
em En
| MEDLINE
| ID: mdl-16943193
ABSTRACT
Calreticulin (CRT) is a multifunctional Ca(2+)-binding molecular chaperone in the endoplasmic reticulum. In mammals, the expression level of CRT differs markedly in a variety of organs and tissues, suggesting that CRT plays a specific role in each cell type. In the present study, we focused on CRT functions in the kidney, where overall expression of CRT is quite low, and established CRT-overexpressing kidney epithelial cell-derived Madin-Darby canine kidney cells by gene transfection. We demonstrated that, in CRT-overexpressing cells, the morphology was apparently changed, and the original polarized epithelial cell phenotype was destroyed. Furthermore, CRT-overexpressing cells showed enhanced migration through Matrigel-coated Boyden chamber wells, compared with controls. E-cadherin expression was significantly suppressed at the protein and transcriptional levels in CRT-overexpressing cells compared with controls. On the other hand, the expression of mesenchymal protein markers, such as N-cadherin and fibronectin, was up-regulated. We also found that the expression of Slug, a repressor of the E-cadherin promoter, was up-regulated by overexpression of CRT through altered Ca(2+) homeostasis, and this led to enhanced binding of Slug to the E-box element in the E-cadherin promoter. Thus, we conclude that CRT regulates the epithelial-mesenchymal transition-like change of cellular phenotype by modulating the Slug/E-cadherin pathway through altered Ca(2+) homeostasis in cells, suggesting a novel function of CRT in cell-cell interaction of epithelial cells.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Caderinas
/
Regulação da Expressão Gênica
/
Calreticulina
/
Células Epiteliais
/
Rim
Limite:
Animals
Idioma:
En
Revista:
J Biol Chem
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Japão