Identification of Sox6 as a regulator of pancreatic cancer development.
J Cell Mol Med
; 22(3): 1864-1872, 2018 03.
Article
em En
| MEDLINE
| ID: mdl-29369542
ABSTRACT
Pancreatic cancer (PC) is an aggressive malignancy associated with a poor prognosis and low responsiveness to chemotherapy and radiotherapy. Most patients with PC have metastatic disease at diagnosis, which partly accounts for the high mortality from this disease. Here, we explored the role of the transcription factor sex-determining region Y-box (Sox) 6 in the invasiveness of PC cells. We showed that Sox6 is down-regulated in patients with PC in association with metastatic disease. Sox6 overexpression suppressed PC cell proliferation and migration in vitro and tumour growth and liver metastasis in vivo. Sox6 inhibited epithelial-mesenchymal transition (EMT), and Akt signalling. Sox6 was shown to interact with the promoter of Twist1, a helix-loop-helix transcription factor involved in the induction of EMT, and to modulate the expression of Twist1 by recruiting histone deacetylase 1 to the promoter of the Twist1 gene. Twist1 overexpression reversed the effect of Sox6 on inhibiting EMT, confirming that the effect of Sox6 on suppressing tumour invasiveness is mediated by the modulation of Twist1 expression. These results suggest a novel mechanism underlying the aggressive behaviour of PC cells and identify potential therapeutic targets for the treatment of PC.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Pancreáticas
/
Proteínas Nucleares
/
Regulação Neoplásica da Expressão Gênica
/
Proteína 1 Relacionada a Twist
/
Fatores de Transcrição SOXD
/
Histona Desacetilase 1
/
Neoplasias Hepáticas
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article