Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 110, Issue 17, Pages 6829-6834Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1217002110
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Funding
- Program for National Natural Scientific Foundation of China [81172059, 30930025, 81272435, 81001125]
- National Basic Research Program of China [2013CB910500]
- New Century Excellent Talents in University Grant [NCET-08-0128]
- Shanghai Municipal Health Bureau [XYQ2011047]
- Shandong Science and Technology Key Program Project [2010GSF10203]
- Shanghai Leading Academic Discipline Project [B110]
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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.
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