Simulated microgravity inhibits the viability and migration of glioma via FAK/RhoA/Rock and FAK/Nek2 signaling

In Vitro Cell Dev Biol Anim. 2019 Apr;55(4):260-271. doi: 10.1007/s11626-019-00334-7. Epub 2019 Feb 28.

Abstract

Due to excessive proliferation and metastasis, glioma is the most common primary tumor in the central nervous system. Previous reports show simulated microgravity (SMG) has the ability to inhibit the proliferation and migration of cancer. The aim of this study was to evaluate the viability and migration of U251 cells in SMG environment. SMG induced apoptosis of U251 cells. The FAK/RhoA/Rock and FAK/Nek2 signaling events were attenuated by SMG to destabilize actin cytoskeleton and centrosome disjunction, which caused G2/M arrest and inhibition of cell viability and migration. Overexpressed FAK reversed SMG-induced inhibition of viability and migration in U251 cells, which increased downstream RhoA/Rock signaling and Nek2. These findings reveal novel pathways of FAK/RhoA/Rock and FAK/Nek2 are affected by SMG, and highlight an opportunity to expand therapeutic options in a variety of settings.

Keywords: FAK; Glioma; Nek2; RhoA/Rock; Simulated microgravity.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement*
  • Cell Survival
  • Cytoskeleton / metabolism
  • Focal Adhesion Kinase 1 / antagonists & inhibitors
  • Focal Adhesion Kinase 1 / metabolism*
  • Glioma / pathology*
  • Humans
  • Models, Biological
  • NIMA-Related Kinases / metabolism*
  • Signal Transduction*
  • Weightlessness Simulation*
  • rho-Associated Kinases / metabolism*
  • rhoA GTP-Binding Protein / metabolism*

Substances

  • Focal Adhesion Kinase 1
  • NEK2 protein, human
  • NIMA-Related Kinases
  • rho-Associated Kinases
  • rhoA GTP-Binding Protein