Functional role of gangliotetraosylceramide in epithelial-to-mesenchymal transition process induced by hypoxia and by TGF-{beta}.
FASEB J
; 24(12): 4889-903, 2010 Dec.
Article
em En
| MEDLINE
| ID: mdl-20720159
ABSTRACT
The epithelial-to-mesenchymal transition (EMT) is a basic cellular process that plays a key role in normal embryonic development and in cancer progression/metastasis. Our previous study indicated that EMT processes of mouse and human epithelial cells induced by TGF-ß display clear reduction of gangliotetraosylceramide (Gg4) and ganglioside GM2, suggesting a close association of glycosphingolipids (GSLs) with EMT. In the present study, using normal murine mammary gland (NMuMG) cells, we found that levels of Gg4 and of mRNA for the UDP-Galß1-3galactosyltransferase-4 (ß3GalT4) gene, responsible for reduction of Gg4, were reduced in EMT induced by hypoxia (â¼1% O(2)) or CoCl(2) (hypoxia mimic), similarly to that for TGF-ß-induced EMT. An increase in the Gg4 level by its exogenous addition or by transfection of the ß3GalT4 gene inhibited the hypoxia-induced or TGF-ß-induced EMT process, including changes in epithelial cell morphology, enhanced motility, and associated changes in epithelial vs. mesenchymal molecules. We also found that Gg4 is closely associated with E-cadherin and ß-catenin. These results suggest that the ß3GalT4 gene, responsible for Gg4 expression, is down-regulated in EMT; and Gg4 has a regulatory function in the EMT process in NMuMG cells, possibly through interaction with epithelial molecules important to maintain epithelial cell membrane organization.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Hipóxia Celular
/
Fator de Crescimento Transformador beta
/
Transição Epitelial-Mesenquimal
/
Gangliosídeos
Limite:
Animals
Idioma:
En
Revista:
FASEB J
Assunto da revista:
BIOLOGIA
/
FISIOLOGIA
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Estados Unidos