BCL-XL directly modulates RAS signalling to favour cancer cell stemness.
Nat Commun
; 8(1): 1123, 2017 10 24.
Article
em En
| MEDLINE
| ID: mdl-29066722
ABSTRACT
In tumours, accumulation of chemoresistant cells that express high levels of anti-apoptotic proteins such as BCL-XL is thought to result from the counter selection of sensitive, low expresser clones during progression and/or initial treatment. We herein show that BCL-XL expression is selectively advantageous to cancer cell populations even in the absence of pro-apoptotic pressure. In transformed human mammary epithelial cells BCL-XL favours full activation of signalling downstream of constitutively active RAS with which it interacts in a BH4-dependent manner. Comparative proteomic analysis and functional assays indicate that this is critical for RAS-induced expression of stemness regulators and maintenance of a cancer initiating cell (CIC) phenotype. Resistant cancer cells thus arise from a positive selection driven by BCL-XL modulation of RAS-induced self-renewal, and during which apoptotic resistance is not necessarily the directly selected trait.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Células-Tronco Neoplásicas
/
Neoplasias da Mama
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Transdução de Sinais
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Regulação Neoplásica da Expressão Gênica
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Proteínas ras
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Proteína bcl-X
Limite:
Animals
/
Female
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Humans
Idioma:
En
Revista:
Nat Commun
Assunto da revista:
BIOLOGIA
/
CIENCIA
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
França