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

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

  • Exp Cell Res. 2025 Apr 1;447(1):114500. doi: 10.1016/j.yexcr.2025.114500.
TzuMin Chen 1,  JenFu Yang 2,  YiHsuan Lin 3,  YuLing Tsai 4,  ChienRui Lai 3,  WenChiuan Tsai 5,  Ying Chen 6
Affiliations

Affiliations

  • 1 Department of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan; Department of Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.
  • 2 Department of Radiation Oncology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
  • 3 Department of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan.
  • 4 Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
  • 5 Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan.
  • 6 Department of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan. Electronic address: ychen0523@mail.ndmctsgh.edu.tw.
PMID: 40058449 DOI: 10.1016/j.yexcr.2025.114500
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.

Keywords

Farnesoid X receptor; Glioblastoma; Invasion; JAK2; Migration; Tight junction.

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