2. Academic Validation
  3. Enhancement of Farnesoid X Receptor Inhibits Migration, Adhesion and Angiogenesis through Proteasome Degradation and VEGF Reduction in Bladder Cancers

Enhancement of Farnesoid X Receptor Inhibits Migration, Adhesion and Angiogenesis through Proteasome Degradation and VEGF Reduction in Bladder Cancers

  • Int J Mol Sci. 2022 May 9;23(9):5259. doi: 10.3390/ijms23095259.
Chien-Rui Lai 1,  Hisao-Hsien Wang 2,  Hsin-Han Chang 1,  Yu-Ling Tsai 3,  Wen-Chiuan Tsai 3,  Chen-Ray Lee 4,  Chih-Ying Changchien 1 5,  Yu-Chen Cheng 1,  Sheng-Tang Wu 6,  Ying Chen 1
Affiliations

Affiliations

  • 1 Department of Biology and Anatomy, National Defense Medical Center, Taipei 11490, Taiwan.
  • 2 Department of Urology, Cheng Hsin General Hospital, Taipei 11490, Taiwan.
  • 3 Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan.
  • 4 Department of Medicine, National Defense Medical Center, Taipei 11490, Taiwan.
  • 5 Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan.
  • 6 Division of Urology, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan.
PMID: 35563650 DOI: 10.3390/ijms23095259
Abstract

(1) Background: Bladder Cancer is a malignant tumor mainly caused by exposure to environmental chemicals, with a high recurrence rate. NR1H4, also known as Farnesoid X Receptor (FXR), acts as a nuclear receptor that can be activated by binding with bile acids, and FXR is highly correlated with the progression of cancers. The aim of this study was to verify the role of FXR in bladder Cancer cells. (2) Methods: A FXR overexpressed system was established to investigate the effect of cell viability, migration, adhesion, and angiogenesis in low-grade TSGH8301 and high-grade T24 cells. (3) Results: After FXR overexpression, the ability of migration, adhesion, invasion and angiogenesis of bladder Cancer cells declined significantly. Focal adhesive complex, MMP2, MMP9, and angiogenic-related proteins were decreased, while FXR was overexpressed in bladder Cancer cells. Moreover, FXR overexpression reduced vascular endothelial growth factor mRNA and protein expression and secretion in bladder Cancer cells. After treatment with the proteosome inhibitor MG132, the migration, adhesion and angiogenesis caused by FXR overexpression were all reversed in bladder Cancer cells. (4) Conclusions: These results may provide evidence on the role of FXR in bladder Cancer, and thus may improve the therapeutic efficacy of urothelial carcinoma in the future.

Keywords

FXR; VEGF; angiogenesis; bladder cancer; invasion; migration; proteasomal degradation; protein half-life.

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