1. Activation of PI3K/Akt pathway by CD133-p85 interaction promotes tumorigenic capacity of glioma stem cells.
- Author
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Yuanyan Wei, Yizhou Jiang, Fei Zou, Yingchao Liu, Shanshan Wang, Nuo Xu, Wenlong Xu, Chunhong Cui, Yang Xing, Ying Liu, Benjin Cao, Chanjuan Liu, Guoqiang Wu, Hong Ao, Xiaobiao Zhang, and Jianhai Jiang
- Subjects
ONCOGENIC viruses ,GLIOMAS ,CANCER stem cells ,PHOSPHORYLATION ,TYROSINE ,PHOSPHOINOSITIDES - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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