Induction of Trop-2 expression through the binding of galectin-3 to MUC1.
Biochem Biophys Res Commun
; 516(1): 44-49, 2019 08 13.
Article
em En
| MEDLINE
| ID: mdl-31196625
ABSTRACT
Both mucin 1 (MUC1) and trophoblast cell surface antigen 2 (Trop-2) are overexpressed in various epithelial tumor cells, and their high expression is correlated with a poor prognosis. Both proteins were expressed in a human breast cancer cell line, MCF-7â¯cells, but neither was in a human colon cancer cell line, HCT116â¯cells. When MUC1 cDNA was introduced into HCT116â¯cells (HCT116/MUC1), expression of Trop-2 was induced. Reciprocally, treatment of MCF-7â¯cells with MUC1 siRNA reduced the level of Trop-2. Mithramycin A, an inhibitor of specificity protein 1 (Sp1) transcription factor, effectively inhibited the expression of Trop-2. Consistently, treatment with Sp1 siRNA reduced the expression of Trop-2. To reveal the relationship between MUC1 and Sp1, coimmunoprecipitation assays were performed. Sp1 was coimmunoprecipitated with MUC1 and the level of coimmunoprecipitated Sp1 increased in relation to the level of induced Trop-2. It is known that galectin-3 is an endogenous ligand of MUC1. Binding of galectin-3 to MUC1 elevated the recruitment of Sp1 to MUC1, and knockdown of galectin-3 reduced the level of Trop-2. These results suggest that the binding of galectin-3 to MUC1 enhances the recruitment of Sp1, leading to promotion of the transcription of Trop-2.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Moléculas de Adesão Celular
/
Regulação para Cima
/
Mucina-1
/
Galectina 3
/
Antígenos de Neoplasias
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Biochem Biophys Res Commun
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Japão