Bcl-3 regulates TGFß signaling by stabilizing Smad3 during breast cancer pulmonary metastasis.
Cell Death Dis
; 7(12): e2508, 2016 12 01.
Article
em En
| MEDLINE
| ID: mdl-27906182
ABSTRACT
Transforming growth factor beta (TGFß) signaling in breast cancer is selectively associated with pulmonary metastasis. However, the underlying mechanisms remain unclear. Here we show that Bcl-3, a member of the IκB family, serves as a critical regulator in TGFß signaling to modulate breast cancer pulmonary metastasis. Bcl-3 expression was significantly associated with metastasis-free survival in breast cancer patients. Bcl-3 deletion inhibited the migration and invasion of breast cancer cells in vitro, as well as breast cancer lung metastasis in vivo. Bcl-3 was required for the expression of downstream TGFß signaling genes that are involved in breast cancer lung metastasis. Bcl-3 knockdown enhanced the degradation of Smad3 but not Smad2 following TGFß treatment. Bcl-3 could bind to Smad3 and prevent the ubiquitination and degradation of Smad3 protein. These results indicate that Bcl-3 serves as a promising target to prevent breast tumor lung metastasis.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
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Neoplasias da Mama
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Transdução de Sinais
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Fator de Crescimento Transformador beta
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Proteínas Proto-Oncogênicas
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Proteína Smad3
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Neoplasias Pulmonares
Limite:
Animals
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Female
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Humans
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article