title: Focal adhesion kinase is required for KSHV vGPCR signaling.
abstract: Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiologic agent of Kaposi's sarcoma, an angiogenic and inflammatory endothelial cell (EC) tumor that is common in areas of high KSHV prevalence. KSHV encodes a pro-angiogenic viral chemokine receptor (vGPCR) that promotes EC growth in vitro and KS-like tumors in mouse models. vGPCR is therefore considered a viral oncogene that plays a crucial role in the pathobiology of KS. In this study, we show that focal adhesion kinase (FAK) becomes activated upon vGPCR expression in primary ECs and that FAK is required for vGPCR-mediated activation of ERK1/2, NFκB, AP-1, and vGPCR-induced migration and inhibition of anoikis. FAK is crucial to cell motility and tumor invasiveness and is a potential therapeutic target in various malignancies. Our data show that via vGPCR, KSHV has evolved a way to constitutively activate FAK signaling.
authors.affiliation: The Department of Medicine, The University of Minnesota, Minneapolis, Minnesota; The Center for Infectious Diseases and Microbiology Translational Research, The University of Minnesota, Minneapolis, Minnesota.
authors.forename: Meilan
authors.initials: M
authors.lastname: He
authors.forename: Thomas
authors.initials: T
authors.lastname: Bakken
authors.forename: Alia
authors.initials: A
authors.lastname: Kassimova
authors.forename: Chris
authors.initials: C
authors.lastname: Boshoff
authors.forename: Nicola
authors.initials: N
authors.lastname: Philpott
authors.forename: Mark L
authors.initials: ML
authors.lastname: Cannon
mesh_terms: D000818:Animals; D023102:Anoikis; D002465:Cell Movement; D017077:Culture Media, Conditioned / Q000737:chemistry; D003599:Cytoskeleton / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology; D005347:Fibroblasts / Q000378:metabolism; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism*; D057809:HEK293 Cells; D019288:Herpesvirus 8, Human / Q000378:metabolism*; D006801:Humans; D016023:Integrins / Q000378:metabolism; D051379:Mice; D009389:Neovascularization, Pathologic; D009857:Oncogenes / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D017077:Culture Media, Conditioned; D016023:Integrins; D043562:Receptors, G-Protein-Coupled; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human