FoxM1 affects adhesive, migratory, and invasive abilities of human retinoblastoma Y-79 cells by targeting matrix metalloproteinase 2.
Acta Biochim Biophys Sin (Shanghai)
; 52(3): 294-301, 2020 Mar 18.
Article
em En
| MEDLINE
| ID: mdl-32152631
ABSTRACT
Forkhead box protein M1 (FoxM1) is an important transcription factor involved in various pathological processes including tumor metastasis. The changes of adhesive, migratory, and invasive abilities are considered as crucial events in tumor metastasis progression. In this study, we aimed to investigate the correlation between FoxM1 and retinoblastoma (Rb) metastasis and to explore the detailed mechanism. Wound healing, cell adhesion, and invasion assays showed that FoxM1 overexpression induced epithelial-mesenchymal transition in Y-79 cells and inhibited adhesion and subsequently promoted metastasis of Y-79 cells, while FoxM1 knockdown showed the opposite effects. A luciferase reporter assay and chromatin immunoprecipitation assay provided evidence that FoxM1 promoted matrix metalloproteinase 2 (MMP2) transcription by directly binding to and promoting MMP2 promoter. MMP2 knockdown by siRNA transfection attenuated cell metastasis of Y-79 cells induced by FoxM1 overexpression. Furthermore, the FoxM1-binding site mapped between -1167 and -1161 bp of the MMP2 promoter was identified. Our results suggested that the FoxM1-MMP2 axis plays an important role in Rb metastasis, which may be a novel target for designing therapeutic regimen to control Rb metastasis.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Retinoblastoma
/
Neoplasias da Retina
/
Metaloproteinase 2 da Matriz
/
Proteína Forkhead Box M1
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Acta Biochim Biophys Sin (Shanghai)
Assunto da revista:
BIOFISICA
/
BIOQUIMICA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
China