Restraining FOXO3-dependent transcriptional BMF activation underpins tumour growth and metastasis of E-cadherin-negative breast cancer.
Cell Death Differ
; 23(9): 1483-92, 2016 09 01.
Article
en En
| MEDLINE
| ID: mdl-27035620
ABSTRACT
Loss of cellular adhesion leads to the progression of breast cancer through acquisition of anchorage independence, also known as resistance to anoikis. Although inactivation of E-cadherin is essential for acquisition of anoikis resistance, it has remained unclear how metastatic breast cancer cells counterbalance the induction of apoptosis without E-cadherin-dependent cellular adhesion. We report here that E-cadherin inactivation in breast cancer cells induces PI3K/AKT-dependent FOXO3 inhibition and identify FOXO3 as a novel and direct transcriptional activator of the pro-apoptotic protein BMF. As a result, E-cadherin-negative breast fail to upregulate BMF upon transfer to anchorage independence, leading to anoikis resistance. Conversely, expression of BMF in E-cadherin-negative metastatic breast cancer cells is sufficient to inhibit tumour growth and dissemination in mice. In conclusion, we have identified repression of BMF as a major cue that underpins anoikis resistance and tumour dissemination in E-cadherin-deficient metastatic breast cancer.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Neoplasias de la Mama
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Cadherinas
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Proteínas Adaptadoras Transductoras de Señales
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Proteína Forkhead Box O3
Límite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Cell Death Differ
Año:
2016
Tipo del documento:
Article
País de afiliación:
Países Bajos