Farnesoid X receptor induction decreases invasion and tumor progression by JAK2/occludin signaling in human glioblastoma cells.

in Experimental cell research by TzuMin Chen, JenFu Yang, YiHsuan Lin, YuLing Tsai, ChienRui Lai, WenChiuan Tsai, Ying Chen

TLDR

  • FXR overexpression inhibits GBM cell migration and invasion, potentially by inhibiting JAK2 and enhancing tight junction protein expression, and may be a promising therapeutic strategy for GBM treatment.

Abstract

Glioblastoma multiforme (GBM) is a brain cancer characterized by low survival and high recurrence rates. Farnesoid X receptor (FXR), a nuclear receptor for bile acids, is expressed at low levels in GBM. This study explores the impact of FXR regulation on GBM cell migration and invasion. Higher FXR expression correlated with increased survival in GBM patients, based on TCGA data. FXR overexpression inhibited cell viability, migration and invasion as well as matrix metalloproteinase 2 (MMP2) activity, while knockdown of FXR exerted the opposite effects. The expression of the tight junction proteins occludin and ZO-1 was enhanced after FXR overexpression. Moreover, a JAK2 activator reversed the migration and invasion of FXR-overexpressing GBM cells. In an animal study, FXR overexpression combined with temozolomide treatment decreased tumor mass, and MMP2 expression and elevated occludin expression in mice. In conclusion, FXR overexpression inhibits the progression of GBM, which may be mediated by inhibiting JAK2 and enhancing tight junction protein expression.

Overview

  • The study explores the impact of Farnesoid X receptor (FXR) regulation on Glioblastoma multiforme (GBM) cell migration and invasion.
  • FXR is a nuclear receptor for bile acids that is expressed at low levels in GBM, but higher FXR expression correlates with increased survival in GBM patients.
  • The study aims to identify the effects of FXR overexpression on GBM cell viability, migration, invasion, and tight junction protein expression, and to investigate the potential mechanisms underlying these effects.

Comparative Analysis & Findings

  • FXR overexpression inhibited cell viability, migration, and invasion as well as matrix metalloproteinase 2 (MMP2) activity, while knockdown of FXR exerted the opposite effects.
  • The expression of the tight junction proteins occludin and ZO-1 was enhanced after FXR overexpression.
  • A JAK2 activator reversed the migration and invasion of FXR-overexpressing GBM cells.

Implications and Future Directions

  • The study suggests that FXR overexpression may be a potential therapeutic strategy for GBM treatment, which may be mediated by inhibiting JAK2 and enhancing tight junction protein expression.
  • Future studies should investigate the optimal dosage and duration of FXR overexpression for optimal treatment outcomes.
  • The combination of FXR overexpression with temozolomide treatment warrants further exploration, as it showed promise in decreasing tumor mass and inhibiting MMP2 expression in animal studies.
Read Full Article