Galectin-3 increases the motility of mouse melanoma cells by regulating matrix metalloproteinase-1 expression
Experimental & Molecular Medicine
;
: 387-393, 2012.
Artigo
em Inglês
| WPRIM
| ID: wpr-57561
ABSTRACT
Although mounting evidence indicates the involvement of galectin-3 in cancer progression and metastasis, the underlying molecular mechanisms remain largely unknown. In this study, we investigated the effect and possible mechanism of galectin-3 on the migration and invasion of B16F10, a metastatic melanoma cell line, in which galectin-3 and matrix metalloproteinase-1 (MMP-1) were both found to be highly expressed. Knockdown of galectin-3 with specific siRNA reduced migration and invasion, which was associated with reduced expression of MMP-1. To further investigate the underlying mechanism, we examined the effect of galectin-3 knockdown on the activity of AP-1, a transcriptional factor regulating MMP-1 expression. We found that galectin-3 directly interacted with AP-1 and facilitated the binding of this complex to the MMP-1 promoter that drives MMP-1 transcription. Moreover, silencing of galectin-3 inhibited binding of fra-1 and c-Jun to promoter sites of MMP-1 gene. Consistent with these in vitro findings, our in vivo study demonstrated that galectin-3 shRNA treatment significantly reduced the total number of mouse lung metastatic nodules. Taken together, galectin-3 facilitates cell migration and invasion in melanoma in vitro and can induce metastasis in vivo, in part through, regulating the transcription activity of AP-1 and thereby up-regulating MMP-1 expression.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Transcrição Gênica
/
Sítios de Ligação
/
Melanoma Experimental
/
Ativação Transcricional
/
Movimento Celular
/
Regiões Promotoras Genéticas
/
Proteínas Proto-Oncogênicas c-fos
/
Fator de Transcrição AP-1
/
Metaloproteinase 1 da Matriz
/
Galectina 3
Limite:
Animais
Idioma:
Inglês
Revista:
Experimental & Molecular Medicine
Ano de publicação:
2012
Tipo de documento:
Artigo
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