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

Lai, Chien-Rui; Wang, Hisao-Hsien; Chang, Hsin‐Han; Tsai, Yu‐Ling; Tsai, Wen‐Chiuan; Lee, Chen-Ray; Changchien, Chih‐Ying; Cheng, Yu‐Chen; Wu, Sheng‐Tang; Chen, Ying

doi:10.3390/ijms23095259

Cited by 7 publications

(5 citation statements)

References 39 publications

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“…In previous studies [ 19 ], we developed a system for overexpressing FXR in NMIBC TSGH8301 and MIBC T24 cells. After FXR overexpression, the intracellular cholesterol content and cholesterol secretion were obviously decreased in both TSGH8301 and T24 cells ( Figure 1 A,B).…”

Section: Resultsmentioning

confidence: 99%

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Farnesoid X Receptor Overexpression Decreases the Migration, Invasion and Angiogenesis of Human Bladder Cancers via AMPK Activation and Cholesterol Biosynthesis Inhibition

Lai

Tsai

et al. 2022

Cancers

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Bladder cancer is one of the most prevailing cancers worldwide. Although treatments for urothelial carcinoma have improved, the rate of recurrence observed in the clinic is still high. The aim of this study was to evaluate whether cholesterol biosynthesis is involved in the effect of Farnesoid X Receptor (FXR) on bladder cancers. FXR overexpression contributed to activation of 5′ AMP-activated protein kinase (AMPK) and decreased cholesterol levels. FXR overexpression reduced cholesterol biosynthesis and secretion by downregulating Sterol Regulatory Element Binding Protein 2 (SREBP2) and 3-Hydroxy-3-Methylglutaryl-CoA Reductase (HMGCR) expression. In addition, an AMPK inhibitor, dorsomorphin, reversed the inhibition of migration, invasion and angiogenesis by FXR overexpression. In a metastatic xenograft animal study, FXR overexpression suppressed bladder cancer lung metastasis by decreasing matrix metalloproteinase-2 (MMP2), SREBP2 and HMGCR expression. Moreover, FXR overexpression combined with atorvastatin treatment an further enhanced the downregulation of the migratory, adhesive, invasive and angiogenic properties in human urothelial carcinoma. In clinical observations, statin administration was associated with better survival rates of early-stage bladder cancer patients. Our results may provide guidance for improving therapeutic strategies for the treatment of urothelial carcinoma.

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Section: Resultsmentioning

confidence: 99%

“…Our previous studies have shown that FXR contributes to bladder cancer cell migration, invasion, and angiogenesis through the proteasomal degradation pathway [ 19 ]. In this study, we aimed to determine whether cholesterol metabolism-related signaling is involved in the induction of FXR expression in human bladder cancer cells.…”

Section: Introductionmentioning

confidence: 99%

Farnesoid X Receptor Overexpression Decreases the Migration, Invasion and Angiogenesis of Human Bladder Cancers via AMPK Activation and Cholesterol Biosynthesis Inhibition

Lai

Tsai

et al. 2022

Cancers

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“…FXR overexpression induces AMPK phosphorylation and decreases cholesterol synthase-related protein expression. Statin usage showed potent enough efficacy to strengthen the enhancement of FXR-inhibited migration, adhesion, and angiogenesis in human urothelial carcinoma cells [ 123 , 124 ].…”

Section: The Regulatory Role Of Tumour Microenvironment and Its Impac...mentioning

confidence: 99%

An Overview of Angiogenesis in Bladder Cancer

2023

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Purpose of the Review Angiogenesis plays a key role in bladder cancer (BC) pathogenesis. In the last two decades, an increasing number of publications depicting a multitude of novel angiogenic molecules and pathways have emerged. The growing complexity necessitates an evaluation of the breadth of current knowledge to highlight key findings and guide future research. Recent Findings Angiogenesis is a dynamic biologic process that is inherently difficult to assess. Clinical assessment of angiogenesis in BCs is advancing with the integration of image analysis systems and dynamic contrast-enhanced and magnetic resonance imaging (DCE-MRI). Tumour-associated macrophages (TAMs) significantly influence the angiogenic process, and further research is needed to assess their potential as therapeutic targets. A rapidly growing list of non-coding RNAs affect angiogenesis in BCs, partly through modulation of vascular endothelial growth factor (VEGF) activity. Vascular mimicry (VM) has been repeatedly associated with increased tumour aggressiveness in BCs. Standardised assays are needed for appropriate identification and quantification of VM channels. Summary This article demonstrates the dynamic and complex nature of the angiogenic process and asserts the need for further studies to deepen our understanding.

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“…However, bile acids, including chenodeoxycholic acid (CDCA), Glycoursodeoxycholic acid (GUDCA), and glycochenodeoxycholic acid (GCDCA), were detected to be upregulated in urine samples of bladder cancer patients compared to healthy controls [ 71 ] . Furthermore, farnesoid X receptor (a nuclear receptor that can be activated by binding with bile acids) was reported to inhibit the migration, invasion, and angiogenesis of bladder cancer in vitro through various mechanisms [ 72 , 73 ] . This reminds us that the bile acids in circulation or urine may partly influence the progression of bladder cancer.…”

Section: Microbiota and Progression Of Bladder Cancermentioning

confidence: 99%

The role of microbiota in tumorigenesis, progression and treatment of bladder cancer

Peng,

Zhuang,

Shen

2023

Microbiome Res Rep

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For decades, the urinary system was regarded as a sterile environment due to the absence of any bacterial growth in clinical standard urine cultures from healthy individuals. However, a diverse array of microbes colonizes the urinary system in small quantities, exhibiting a variable compositional signature influenced by differences in sex, age, and pathological state. Increasing pieces of evidence suggest microbiota exists in tumor tissue and plays a crucial role in tumor microenvironment based on research in multiple cancer models. Current studies about microbiota and bladder cancer have preliminarily characterized the bladder cancer-related microbiota, but how the microbiota influences the biological behavior of bladder cancer remains unclarified. This review summarizes the characteristics of microbiota in bladder cancer, aims to propose possible mechanisms that microbiota acts in tumorigenesis and progression of bladder cancer based on advances in gut microbiota, and discusses the potential clinical application of microbiota in bladder cancer.

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

Cited by 7 publications

References 39 publications

Farnesoid X Receptor Overexpression Decreases the Migration, Invasion and Angiogenesis of Human Bladder Cancers via AMPK Activation and Cholesterol Biosynthesis Inhibition

Farnesoid X Receptor Overexpression Decreases the Migration, Invasion and Angiogenesis of Human Bladder Cancers via AMPK Activation and Cholesterol Biosynthesis Inhibition

An Overview of Angiogenesis in Bladder Cancer

The role of microbiota in tumorigenesis, progression and treatment of bladder cancer

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