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

作者：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^*

来源：Proceedings of the National Academy of Sciences of the United States of America, 2013, 110(17): 6829-6834.

DOI：10.1073/pnas.1217002110

• PLASMA-MEMBRANE PROTRUSIONS
• PROTEIN-KINASE B
• HEMATOPOIETIC STEM
• PHOSPHATIDYLINOSITOL 3-KINASE
• EPITHELIAL-CELLS
• NEURAL PROGENITORS
• FACTOR-RECEPTOR
• BRAIN CANCER
• AKT
• SRC

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 stemcell (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.

• 出版日期2013-4-23
• 单位复旦大学; 山东大学; 山东省立医院