CCN5, a novel transcriptional repressor of the transforming growth factor ß signaling pathway.
Mol Cell Biol
; 31(7): 1459-69, 2011 Apr.
Article
em En
| MEDLINE
| ID: mdl-21262769
ABSTRACT
CCN5 is a member of the CCN (connective tissue growth factor/cysteine-rich 61/nephroblastoma overexpressed) family and was identified as an estrogen-inducible gene in estrogen receptor-positive cell lines. However, the role of CCN5 in breast carcinogenesis remains unclear. We report here that the CCN5 protein is localized mostly in the cytoplasm and in part in the nucleus of human tumor breast tissue. Using a heterologous transcription assay, we demonstrate that CCN5 can act as a transcriptional repressor presumably through association with histone deacetylase 1 (HDAC1). Microarray gene expression analysis showed that CCN5 represses expression of genes associated with epithelial-mesenchymal transition (EMT) as well as expression of key components of the transforming growth factor ß (TGF-ß) signaling pathway, prominent among them TGF-ßRII receptor. We show that CCN5 is recruited to the TGF-ßRII promoter, thereby providing a mechanism by which CCN5 restricts transcription of the TGF-ßRII gene. Consistent with this finding, CCN5, we found, functions to suppress TGF-ß-induced transcriptional responses and invasion that is concomitant with EMT. Thus, our data uncovered CCN5 as a novel transcriptional repressor that plays an important role in regulating tumor progression functioning, at least in part, by inhibiting the expression of genes involved in the TGF-ß signaling cascade that is known to promote EMT.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Repressoras
/
Fatores de Transcrição
/
Transcrição Gênica
/
Transdução de Sinais
/
Fator de Crescimento Transformador beta
/
Peptídeos e Proteínas de Sinalização Intercelular
Tipo de estudo:
Prognostic_studies
Limite:
Female
/
Humans
Idioma:
En
Revista:
Mol Cell Biol
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
França