The Sal-like 4 - integrin α6ß1 network promotes cell migration for metastasis via activation of focal adhesion dynamics in basal-like breast cancer cells.
Biochim Biophys Acta Mol Cell Res
; 1864(1): 76-88, 2017 Jan.
Article
em En
| MEDLINE
| ID: mdl-27773610
ABSTRACT
During metastasis, cancer cell migration is enhanced. However, the mechanisms underlying this process remain elusive. Here, we addressed this issue by functionally analyzing the transcription factor Sal-like 4 (SALL4) in basal-like breast cancer cells. Loss-of-function studies of SALL4 showed that this transcription factor is required for the spindle-shaped morphology and the enhanced migration of cancer cells. SALL4 also up-regulated integrin gene expression. The impaired cell migration observed in SALL4 knockdown cells was restored by overexpression of integrin α6 and ß1. In addition, we clarified that integrin α6 and ß1 formed a heterodimer. At the molecular level, loss of the SALL4 - integrin α6ß1 network lost focal adhesion dynamics, which impairs cell migration. Over-activation of Rho is known to inhibit focal adhesion dynamics. We observed that SALL4 knockdown cells exhibited over-activation of Rho. Aberrant Rho activation was suppressed by integrin α6ß1 expression, and pharmacological inhibition of Rho activity restored cell migration in SALL4 knockdown cells. These results indicated that the SALL4 - integrin α6ß1 network promotes cell migration via modulation of Rho activity. Moreover, our zebrafish metastasis assays demonstrated that this gene network enhances cell migration in vivo. Our findings identify a potential new therapeutic target for the prevention of metastasis, and provide an improved understanding of cancer cell migration.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
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Neoplasias da Mama
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Regulação Neoplásica da Expressão Gênica
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Integrina beta1
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Integrina alfa6
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Células Epiteliais
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Biochim Biophys Acta Mol Cell Res
Ano de publicação:
2017
Tipo de documento:
Article