Activation of PI3K/Akt pathway by CD133-p85 interaction promotes tumorigenic capacity of glioma stem cells.
Proc Natl Acad Sci U S A
; 110(17): 6829-34, 2013 Apr 23.
Article
em En
| MEDLINE
| ID: mdl-23569237
ABSTRACT
The biological significance of a known normal and cancer stem cell marker CD133 remains elusive. We now demonstrate that the phosphorylation of tyrosine-828 residue in CD133 C-terminal cytoplasmic domain mediates direct interaction between CD133 and phosphoinositide 3-kinase (PI3K) 85 kDa regulatory subunit (p85), resulting in preferential activation of PI3K/protein kinase B (Akt) pathway in glioma stem cell (GSC) relative to matched nonstem cell. CD133 knockdown potently inhibits the activity of PI3K/Akt pathway with an accompanying reduction in the self-renewal and tumorigenicity of GSC. The inhibitory effects of CD133 knockdown could be completely rescued by expression of WT CD133, but not its p85-binding deficient Y828F mutant. Analysis of glioma samples reveals that CD133 Y828 phosphorylation level is correlated with histopathological grade and overlaps with Akt activation. Our results identify the CD133/PI3K/Akt signaling axis, exploring the fundamental role of CD133 in glioma stem cell behavior.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Peptídeos
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Células-Tronco Neoplásicas
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Glicoproteínas
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Transdução de Sinais
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Antígenos CD
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Transformação Celular Neoplásica
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Classe Ia de Fosfatidilinositol 3-Quinase
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Glioma
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article