期刊
VIROLOGY JOURNAL
卷 11, 期 -, 页码 -出版社
BIOMED CENTRAL LTD
DOI: 10.1186/s12985-014-0218-8
关键词
Kaposi's sarcoma-associated herpesvirus; Wnt/beta-catenin signaling; Angiogenesis
类别
资金
- National Institutes of Health [R21HD076283, R01HD51998, P20GM103424]
Background: KSHV is a tumorigenic.-herpesvirus that has been identified as the etiologic agent of Kaposi's sarcoma (KS), a multifocal highly vascularized neoplasm that is the most common malignancy associated with acquired immunodeficiency syndrome (AIDS). The virus encodes a constitutively active chemokine receptor homologue, vGPCR that possesses potent angiogenic and tumorigenic properties, and is critical for KSHV pathobiology. To date, a number of signaling pathways have been identified as key in mediating vGPCR oncogenic potential. Findings: In this study, we identify a novel pathway, the Wnt/beta-catenin pathway, which is dysregulated by vGPCR expression in endothelial cells. Expression of vGPCR in endothelial cells enhances the nuclear accumulation of beta-catenin, that correlates with an increase in beta-catenin transcriptional activity. Activation of beta-catenin signaling by vGPCR is dependent on the PI3K/Akt pathway, as treatment of vGPCR-expressing cells with a pharmacological inhibitor of PI3K, leads to a decreased activation of a beta-catenin-driven reporter, a significant decrease in expression of beta-catenin target genes, and reduced endothelial tube formation. Conclusions: Given the critical role of Wnt/beta-catenin signaling in angiogenesis and tumorigenesis, the findings from this study suggest a novel mechanism in KSHV-induced malignancies.
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