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

Lai, Chien-Rui; Tsai, Yu‐Ling; Tsai, Wen‐Chiuan; Chen, Tzu-Min; Chang, Hsin‐Han; Changchien, Chih‐Ying; Wu, Sheng‐Tang; Wang, Hisao-Hsien; Chen, Ying; Lin, Yu Huei

doi:10.3390/cancers14184398

Cited by 10 publications

(4 citation statements)

References 41 publications

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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: Metabolic Derangements and Angiogenesis In Bladder Cancermentioning

confidence: 98%

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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Section: Metabolic Derangements and Angiogenesis In Bladder Cancermentioning

confidence: 98%

An Overview of Angiogenesis in Bladder Cancer

2023

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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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“…In bladder carcinoma, FXR inhibits cancer cell migration, adhesion, and angiogenesis through proteasome degradation, VEGF reduction, AMPK activation, and cholesterol biosynthesis inhibition [ 137 , 138 ]. Consistent with the in vitro data, FXR expression was downregulated in human bladder cancer tissues, compared to the adjacent normal tissues, and a higher expression of FXR was significantly associated with a better clinical outcome [ 138 ].…”

Section: Farnesoid X Receptor (Fxr) In Cancermentioning

confidence: 99%

Targeting Farnesoid X Receptor in Tumor and the Tumor Microenvironment: Implication for Therapy

Nenkov,

Shi,

et al. 2023

IJMS

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The farnesoid-X receptor (FXR), a member of the nuclear hormone receptor superfamily, can be activated by bile acids (BAs). BAs binding to FXR activates BA signaling which is important for maintaining BA homeostasis. FXR is differentially expressed in human organs and exists in immune cells. The dysregulation of FXR is associated with a wide range of diseases including metabolic disorders, inflammatory diseases, immune disorders, and malignant neoplasm. Recent studies have demonstrated that FXR influences tumor cell progression and development through regulating oncogenic and tumor-suppressive pathways, and, moreover, it affects the tumor microenvironment (TME) by modulating TME components. These characteristics provide a new perspective on the FXR-targeted therapeutic strategy in cancer. In this review, we have summarized the recent research data on the functions of FXR in solid tumors and its influence on the TME, and discussed the mechanisms underlying the distinct function of FXR in various types of tumors. Additionally, the impacts on the TME by other BA receptors such as takeda G protein-coupled receptor 5 (TGR5), sphingosine-1-phosphate receptor 2 (S1PR2), and muscarinic receptors (CHRM2 and CHRM3), have been depicted. Finally, the effects of FXR agonists/antagonists in a combination therapy with PD1/PD-L1 immune checkpoint inhibitors and other anti-cancer drugs have been addressed.

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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

Cited by 10 publications

References 41 publications

An Overview of Angiogenesis in Bladder Cancer

An Overview of Angiogenesis in Bladder Cancer

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

Targeting Farnesoid X Receptor in Tumor and the Tumor Microenvironment: Implication for Therapy

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