DLX4 upregulates TWIST and enhances tumor migration, invasion and metastasis.
Int J Biol Sci
; 8(8): 1178-87, 2012.
Article
em En
| MEDLINE
| ID: mdl-23091415
ABSTRACT
The distal-less homeobox gene 4 (DLX4) is a member of the DLX family of homeobox genes. Although absent from most normal adult tissues, DLX4 is widely expressed in leukemia, lung, breast, ovarian and prostate cancers. However the molecular targets, mechanisms and pathways that mediate the role of DLX4 in tumor metastasis are poorly understood. In this study, we found that DLX4 induces cancer cells to undergo epithelial to mesenchymal transition (EMT) through TWIST. Overexpression of DLX4 increased expression of TWIST expression in cancer cell lines, resulting in increased migratory and invasive capacity. Likewise, knocking down expression of DLX4 decreased TWIST expression and the migration ability of cancer cell lines. DLX4 bound to regulatory regions of the TWIST gene. Both western blotting and immunohistochemistry staining showed that the expression of DLX4 and TWIST are correlated in most of breast tumors. Taken together, these data from both cell models and tumor tissues demonstrate that DLX4 not only upregulates TWIST expression but also induces EMT and tumor metastasis. Altogether, we propose a new pathway in which DLX4 drives expression of TWIST to promote EMT, cancer migration, invasion and metastasis.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
Neoplasias da Mama
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Regulação Neoplásica da Expressão Gênica
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Movimento Celular
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Proteínas de Homeodomínio
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Proteína 1 Relacionada a Twist
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Transição Epitelial-Mesenquimal
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Invasividade Neoplásica
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Metástase Neoplásica
Tipo de estudo:
Prognostic_studies
Limite:
Female
/
Humans
Idioma:
En
Revista:
Int J Biol Sci
Ano de publicação:
2012
Tipo de documento:
Article