title: Alpha-synuclein contributes to malignant progression of human meningioma via the Akt/mTOR pathway.
abstract: BACKGROUND
  The aim of this study is to explore the expression of alpha-synuclein (α-synuclein) in benign, atypical, and anaplastic meningiomas and determine its role in the malignant progression of meningiomas.
  
  
  METHODS
  Expression of α-synuclein was measured in 44 meningioma samples by real-time PCR analysis. The effects of overexpression or knockdown of α-synuclein on meningioma cell growth, invasiveness, and tumorigenicity were determined.
  
  
  RESULTS
  Atypical and anaplastic meningiomas displayed significantly greater levels of α-synuclein mRNA, relative to benign tumors. Depletion of α-synuclein decreased cell proliferation and colony formation and promoted apoptosis in IOMM-Lee meningioma cells, whereas overexpression of α-synuclein facilitated cell proliferation and colony formation in CH-157MN meningioma cells. Silencing of α-synuclein attenuated IOMM-Lee cell migration and invasion. In contrast, ectopic expression of α-synuclein increased the invasiveness of CH-157MN cells. In vivo studies further demonstrated that downregulation of α-synuclein significantly retarded meningioma growth in nude mice. At the molecular level, the phosphorylation levels of Akt, mTOR, p70S6K and 4EBP were significantly decreased in α-synuclein-depleted IOMM-Lee cells.
  
  
  CONCLUSIONS
  In conclusion, α-synuclein upregulation contributes to aggressive phenotypes of meningiomas via the Akt/mTOR pathway and thus represents a potential therapeutic target for malignant meningiomas.
authors.affiliation: Department of Neurosurgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, No.164 Lanxi Road, Shanghai, 200062 China.
authors.forename: Yiqin
authors.initials: Y
authors.lastname: Ge
authors.affiliation: Department of Neurosurgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, No.164 Lanxi Road, Shanghai, 200062 China.
authors.forename: Kan
authors.initials: K
authors.lastname: Xu
keywords: Akt/mTOR signaling; Growth; Invasion; Meningioma; α-Synuclein