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Alpha-synuclein contributes to malignant progression of human meningioma via the Akt/mTOR pathway

Yiqin Ge1, Kan Xu1

  • 1Department of Neurosurgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, No.164 Lanxi Road, Shanghai, 200062 China.

Cancer Cell International
|November 30, 2016
PubMed
Abstract

Insights

Alpha-synuclein (α-synuclein) is upregulated in aggressive meningiomas, driving malignant progression. Targeting α-synuclein may offer a new therapeutic strategy for these brain tumors.

Area of Science:

  • Neuro-oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Meningiomas are tumors arising from the meninges.
  • Malignant progression involves increased cellularity, atypia, and anaplasia.
  • The role of alpha-synuclein (α-synuclein) in meningioma tumorigenesis is not well understood.

Purpose of the Study:

  • To investigate α-synuclein expression in different grades of meningiomas.
  • To determine the functional role of α-synuclein in meningioma cell behavior and tumor growth.
  • To explore the molecular pathways involved in α-synuclein-mediated meningioma progression.

Main Methods:

  • Real-time PCR analysis of α-synuclein mRNA in 44 meningioma samples.
  • In vitro studies assessing the impact of α-synuclein manipulation on cell proliferation, apoptosis, migration, and invasion.
  • In vivo xenograft studies in nude mice to evaluate tumor growth.
  • Western blot analysis to assess signaling pathway activation.

Main Results:

  • Atypical and anaplastic meningiomas showed significantly higher α-synuclein mRNA levels than benign tumors.
  • α-synuclein knockdown reduced proliferation, colony formation, and invasion, while promoting apoptosis in meningioma cells.
  • α-synuclein overexpression enhanced proliferation, colony formation, and invasion.
  • Downregulation of α-synuclein suppressed tumor growth in vivo and reduced Akt/mTOR pathway activation.

Conclusions:

  • α-synuclein upregulation is associated with aggressive meningioma phenotypes.
  • α-synuclein promotes meningioma cell proliferation, invasion, and survival.
  • The Akt/mTOR pathway is implicated in α-synuclein-driven meningioma progression.
  • α-synuclein represents a potential therapeutic target for malignant meningiomas.
Keywords:
Akt/mTOR signalingGrowthInvasionMeningiomaα-Synuclein

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