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Focal adhesion kinase is required for KSHV vGPCR signaling
Author(s) -
He Meilan,
Bakken Thomas,
Kassimova Alia,
Boshoff Chris,
Philpott Nicola,
Can Mark L.
Publication year - 2012
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.20790
Subject(s) - biology , focal adhesion , signal transduction , cancer research , microbiology and biotechnology , kinase , g protein coupled receptor , kaposi's sarcoma associated herpesvirus , immunology , virus , herpesviridae , viral disease
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. Mol. Carcinog. © 2011 Wiley Periodicals, Inc.