title: Activation of PI3K/Akt pathway by CD133-p85 interaction promotes tumorigenic capacity of glioma stem cells.
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.
authors.affiliation: Key Laboratory of Glycoconjuates Research, Ministry of Public Health, Department of Biochemistry and Molecular Biology, Shanghai Medical College of Fudan University, Shanghai 200032, People's Republic of China.
authors.forename: Yuanyan
authors.initials: Y
authors.lastname: Wei
authors.forename: Yizhou
authors.initials: Y
authors.lastname: Jiang
authors.forename: Fei
authors.initials: F
authors.lastname: Zou
authors.forename: Yingchao
authors.initials: Y
authors.lastname: Liu
authors.forename: Shanshan
authors.initials: S
authors.lastname: Wang
authors.forename: Nuo
authors.initials: N
authors.lastname: Xu
authors.forename: Wenlong
authors.initials: W
authors.lastname: Xu
authors.forename: Chunhong
authors.initials: C
authors.lastname: Cui
authors.forename: Yang
authors.initials: Y
authors.lastname: Xing
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Benjin
authors.initials: B
authors.lastname: Cao
authors.forename: Chanjuan
authors.initials: C
authors.lastname: Liu
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Wu
authors.forename: Hong
authors.initials: H
authors.lastname: Ao
authors.forename: Xiaobiao
authors.initials: X
authors.lastname: Zhang
authors.forename: Jianhai
authors.initials: J
authors.lastname: Jiang
mesh_terms: D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D058543:Class Ia Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D005910:Glioma / Q000378:metabolism / Q000503:physiopathology*; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D020125:Mutation, Missense / Q000235:genetics; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000502:physiology*; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse; D058543:Class Ia Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt