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Analyzing Murine Schwann Cell Development Along Growing Axons
09:46

Analyzing Murine Schwann Cell Development Along Growing Axons

Published on: November 21, 2012

Axl/Gas6/NFκB signalling in schwannoma pathological proliferation, adhesion and survival

S Ammoun1, L Provenzano1, L Zhou1

  • 1Clinical Neurobiology, Institute of Translational and Stratified Medicine, Plymouth University Peninsula Schools of Medicine and Dentistry, Plymouth, UK.

Oncogene
|January 16, 2013
PubMed

Insights

The Axl/FAK/Src/NFκB pathway is overactive in merlin-deficient schwannoma tumors, driving cancer growth and survival. Targeting this pathway offers a promising therapeutic strategy for these challenging tumors.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • TAM family receptor tyrosine kinases (Tyro3, Axl, Mer) are implicated in cancer progression and multidrug resistance.
  • Merlin deficiency, due to mutations in the merlin gene, leads to nervous system tumors like schwannomas, which are often chemotherapy-resistant.
  • Previous studies indicated TAM receptor overexpression in schwannoma tissues and identified Axl as a potential therapeutic target in merlin-deficient tumors.

Purpose of the Study:

  • To investigate the role and activation of the Axl receptor and its ligand Gas6 in merlin-deficient schwannoma.
  • To elucidate the downstream signaling pathways regulated by Gas6/Axl in schwannoma cells.
  • To evaluate the Axl/FAK/Src/NFκB pathway as a potential therapeutic target for schwannoma.

Main Methods:

  • Analysis of Axl receptor and Gas6 expression and activation in human schwannoma primary cells and normal Schwann cells.
  • Assessment of Gas6's effects on schwannoma cell proliferation, adhesion, and survival.
  • Investigation of the signaling molecules recruited upon Gas6/Axl stimulation, including Src, FAK, and NFκB.
  • Determination of NFκB-mediated downstream targets such as survivin, cyclin D1, and FAK.

Main Results:

  • Significant overexpression and activation of Axl receptor and its ligand Gas6 were observed in human schwannoma cells compared to normal Schwann cells.
  • Gas6 demonstrated mitogenic effects, enhancing schwannoma cell-matrix adhesion and survival through Axl signaling.
  • Activation of the Gas6/Axl pathway led to the recruitment of Src, FAK, and NFκB.
  • NFκB was found to mediate the overexpression of survivin, cyclin D1, and FAK, contributing to enhanced cell survival, adhesion, and proliferation.

Conclusions:

  • The Axl/FAK/Src/NFκB signaling pathway is critically involved in the progression of merlin-deficient schwannoma.
  • Targeting the Axl receptor and its downstream signaling components presents a viable therapeutic strategy for schwannoma and other merlin-deficient tumors.

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