Details

Autor(en) / Beteiligte

• Wei, Yuanyan
• Jiang, Yizhou
• Zou, Fei
• Liu, Yingchao
• Wang, Shanshan
• Xu, Nuo
• Xu, Wenlong
• Cui, Chunhong
• Xing, Yang
• Liu, Ying
• Cao, Benjin
• Liu, Chanjuan
• Wu, Guoqiang
• Ao, Hong
• Zhang, Xiaobiao
• Jiang, Jianhai

Titel

Activation of PI3K/Akt pathway by CD133-p85 interaction promotes tumorigenic capacity of glioma stem cells

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2013-04, Vol.110 (17), p.6829-6834

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2013

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 CD 133, 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.