title: Kaposi's sarcoma-associated herpesvirus G-protein coupled receptor activates the canonical Wnt/β-catenin signaling pathway.
abstract: BACKGROUND
  KSHV is a tumorigenic γ-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.
  
  
  RESULTS
  In this study, we identify a novel pathway, the Wnt/β-catenin pathway, which is dysregulated by vGPCR expression in endothelial cells. Expression of vGPCR in endothelial cells enhances the nuclear accumulation of β-catenin, that correlates with an increase in β-catenin transcriptional activity. Activation of β-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 β-catenin-driven reporter, a significant decrease in expression of β-catenin target genes, and reduced endothelial tube formation.
  
  
  CONCLUSIONS
  Given the critical role of Wnt/β-catenin signaling in angiogenesis and tumorigenesis, the findings from this study suggest a novel mechanism in KSHV-induced malignancies.
authors.affiliation: Department of Microbiology and Immunology, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA, USA. Magdalena_Angelova@hms.harvard.edu.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Angelova
authors.affiliation: Department of Microbiology and Immunology, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA, USA. mferris@tulane.edu.
authors.forename: MaryBeth
authors.initials: M
authors.lastname: Ferris
authors.affiliation: Department of Obstetrics and Gynecology, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA, USA. kswan1@tulane.edu.
authors.forename: Kenneth F
authors.initials: KF
authors.lastname: Swan
authors.affiliation: Biology Department, Xavier University, 1 Drexel Drive, New Orleans, LA, USA. hmcferri@xula.edu.
authors.forename: Harris E
authors.initials: HE
authors.lastname: McFerrin
authors.affiliation: Department of Obstetrics and Gynecology, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA, USA. pridjian@tulane.edu.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Pridjian
authors.affiliation: Department of Microbiology and Immunology, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA, USA. Cmorris2@tulane.edu.
authors.forename: Cindy A
authors.initials: CA
authors.lastname: Morris
authors.affiliation: Department of Microbiology and Immunology, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA, USA. dsulliva@tulane.edu.
authors.forename: Deborah E
authors.initials: DE
authors.lastname: Sullivan
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000821:virology; D019288:Herpesvirus 8, Human / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D008819:Mice, Nude; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D060449:Wnt Signaling Pathway
chemical_list: D043562:Receptors, G-Protein-Coupled