Activation of PI3K/Akt pathway by CD133-p85 interaction promotes tumorigenic capacity of glioma stem cells
Y Wei, Y Jiang, F Zou, Y Liu, S Wang… - Proceedings of the …, 2013 - National Acad Sciences
Y Wei, Y Jiang, F Zou, Y Liu, S Wang, N Xu, W Xu, C Cui, Y Xing, Y Liu, B Cao, C Liu, G Wu…
Proceedings of the National Academy of Sciences, 2013•National Acad SciencesThe 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 …
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 …
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.
National Acad Sciences