AI Article Synopsis
- The Kaposi's sarcoma-associated herpesvirus G-protein-coupled receptor (vGPCR) plays a crucial role in the development of Kaposi's sarcoma, with studies suggesting that 1α,25(OH)D and its analog TX 527 can inhibit cell growth in cells expressing vGPCR.
- Research aimed to explore whether these compounds target the Wnt/β-catenin signaling pathway, which is known to be activated by vGPCR.
- Results demonstrated that treatment with 1α,25(OH)D or TX 527 led to reduced activation of the Wnt/β-catenin pathway and suggested a potential for these compounds as chemotherapeutic agents against the cancer.
Article Abstract
The Kaposi's sarcoma-associated herpesvirus G-protein-coupled receptor (vGPCR) is a key molecule in the pathogenesis of Kaposi's sarcoma. We have previously demonstrated that 1α,25(OH)D or its less calcemic analog TX 527 exerts antiproliferative effects in endothelial cells stable expressing vGPCR. Since it is well documented that vGPCR activates the canonical Wnt/β-catenin signaling pathway, the aim of this study was to evaluate if Wnt/β-catenin cascade is target of 1α,25(OH)D or TX 527 as part of their antineoplastic mechanism. Firstly, Western blot studies showed an increase in β-catenin protein levels in a dose and time dependent manner; and when VDR was knockdown, β-catenin protein levels were significantly decreased. Secondly, β-catenin localization, investigated by immunofluorescence and subcellular fractionation techniques, was found increased in the nucleus and plasma membrane after 1α,25(OH)D treatment. VE-cadherin protein levels were also increased in the plasma membrane fraction. Furthermore, β-catenin interaction with VDR was observed by co-immunoprecipitation and mRNA expression of β-catenin target genes was found decreased. Finally, DKK-1, the extracellular inhibitor of Wnt/β-catenin pathway, showed an initial upregulation of mRNA expression. Altogether, the results obtained by different techniques revealed a downregulation of Wnt/β-catenin cascade after 1α,25(OH)D or TX 527 treatment, showing the foundation for a potential chemotherapeutic agent.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.tiv.2019.104748 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Segetalin B promotes bone formation in ovariectomized mice by activating PLD1/SIRT1 signaling to inhibit γ-secretase-mediated Notch1 overactivation.
J Steroid Biochem Mol Biol
December 2024
Department of Rehabilitation Medicine, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China. Electronic address:
Segetalin B (SB) has shown promise in mitigating osteoporosis in ovariectomized (OVX) mice, though its underlying mechanisms remain unclear. This study investigates how SB promotes bone formation through Phospholipase D1 (PLD1) activation in OVX models. In vitro, bone marrow-derived mesenchymal stem cells (BMSCs) from OVX mice were cultured for osteogenic differentiation.
View Article and Find Full Text PDFhijacks the tumor microenvironment in liver cancer cells in a multifaceted approach: A falling row of dominoes.
World J Gastroenterol
December 2024
Department of Gastroenterology, University of Balamand, Beirut 3187, Beyrouth, Lebanon.
(. ) is widely used in traditional Chinese medicine due to its anti-tumor effects. .
View Article and Find Full Text PDFDysregulation of GAS5-miRNA-Mediated Signaling Pathways in Cancer Pathobiology: A Comprehensive Exploration of Pathways Influenced by this Axis.
Biochem Genet
December 2024
College of Pharmacy, The Islamic University, Najaf, Iraq.
The long non-coding RNA Growth Arrest-Specific 5 (GAS5) is pivotal in modulating key signaling pathways by functioning as a molecular sponge for microRNAs (miRNAs). GAS5 is notably recognized for its antitumor properties, primarily through its ability to sequester oncogenic miRNAs, thereby influencing critical pathways such as p53, Wnt/β-catenin, and PI3K/Akt, all of which are integral to cell proliferation, apoptosis, and metastasis. The disruption of GAS5-miRNA interactions has been implicated in various malignancies, reinforcing its potential as both a biomarker and a therapeutic target.
View Article and Find Full Text PDFImpact of Hedgehog modulators on signaling pathways in primary murine and human hepatocytes in vitro: insights into liver metabolism.
Arch Toxicol
December 2024
Faculty of Medicine, Rudolf Schönheimer Institute of Biochemistry, Leipzig University, Leipzig, Germany.
The Hedgehog (Hh) signaling pathway is essential for maintaining homeostasis during embryogenesis and in adult tissues. In the liver, dysregulation of this pathway often leads to liver cancer development. Recent studies also suggest that disturbances in the Hh pathway can affect liver metabolism in healthy livers through interactions with other signaling pathways, such as the Wnt/β-catenin pathway.
View Article and Find Full Text PDFDNA methylation patterns of circadian and ultradian genes are altered in the peripheral blood of patients with hidradenitis suppurativa.
Front Immunol
December 2024
Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy.
Background: Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition that affects hair follicles in areas with apocrine sweat glands, such as the underarms, groin, and buttocks. The pathogenesis of HS is not fully understood, but considering the key role played by the biological clock in the control of immune/inflammatory processes the derangement of circadian and ultradian pathways could be hypothesized.
Methods: We analyzed genome-wide DNA methylation patterns in peripheral blood from 24 HS cases and 24 controls using the Infinium HumanMethylation450 BeadChip array (Illumina), followed by bioinformatics and statistical analyses.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!