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Sci. Signal., 3 August 2010
Vol. 3, Issue 133, p. ra58
[DOI: 10.1126/scisignal.2001180]


Editor's Summary

A Viral Pathway to Tumor Development
Human cytomegalovirus (HCMV), a widespread human herpesvirus that persists in a latent form, is associated with pathological processes in immunocompromised hosts and has been implicated in the development of several forms of cancer, including glioblastoma. HCMV encodes a G protein–coupled receptor, US28, that resembles a chemokine receptor and constitutively activates signaling pathways associated with cell proliferation. Slinger et al. expressed US28 in cultured cells to explore the mechanisms through which it could promote tumor development. They found that US28 stimulated the production and secretion of both vascular endothelial growth factor (VEGF) and the cytokine interleukin-6 (IL-6) and defined a signaling pathway whereby US28 increased cell proliferation through IL-6–dependent activation of the JAK1-STAT3 axis. IL-6 is itself a target of STAT3, leading the authors to propose that US28-dependent production and secretion of IL-6 and consequent autocrine and paracrine STAT3 activation lead to establishment of a positive feedback loop that promotes proliferation of both infected and neighboring cells. Analyses of human glioblastoma tissue revealed US28 and activated STAT3 in cells lining blood vessels, suggesting that US28 may play a role in tumor vascularization.

Citation: E. Slinger, D. Maussang, A. Schreiber, M. Siderius, A. Rahbar, A. Fraile-Ramos, S. A. Lira, C. Söderberg-Nauclér, M. J. Smit, HCMV-Encoded Chemokine Receptor US28 Mediates Proliferative Signaling Through the IL-6–STAT3 Axis. Sci. Signal. 3, ra58 (2010).

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F. Bachelerie, A. Ben-Baruch, A. M. Burkhardt, C. Combadiere, J. M. Farber, G. J. Graham, R. Horuk, A. H. Sparre-Ulrich, M. Locati, A. D. Luster, et al. (2014)
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Z. Khan, K.-C. Yaiw, V. Wilhelmi, H. Lam, A. Rahbar, G. Stragliotto, and C. Soderberg-Naucler (2014)
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J. M. Reitsma, H. Sato, M. Nevels, S. S. Terhune, and C. Paulus (2013)
J. Virol. 87, 10763-10776
   Abstract »    Full Text »    PDF »
Cytomegalovirus Contributes to Glioblastoma in the Context of Tumor Suppressor Mutations.
R. L. Price, J. Song, K. Bingmer, T. H. Kim, J.-Y. Yi, M. O. Nowicki, X. Mo, T. Hollon, E. Murnan, C. Alvarez-Breckenridge, et al. (2013)
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S. M. Kim, O.-J. Kwon, Y. K. Hong, J. H. Kim, F. Solca, S.-J. Ha, R. A. Soo, J. G. Christensen, J. H. Lee, and B. C. Cho (2012)
Mol. Cancer Ther. 11, 2254-2264
   Abstract »    Full Text »    PDF »
Consensus on the role of human cytomegalovirus in glioblastoma.
K. Dziurzynski, S. M. Chang, A. B. Heimberger, R. F. Kalejta, S. R. McGregor Dallas, M. Smit, L. Soroceanu, C. S. Cobbs, and the HCMV and Gliomas Symposium (2012)
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   Abstract »    Full Text »    PDF »
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P. Ranganathan, P. A. Clark, J. S. Kuo, M. S. Salamat, and R. F. Kalejta (2012)
J. Virol. 86, 854-864
   Abstract »    Full Text »    PDF »
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N. Sen, X. Che, J. Rajamani, L. Zerboni, P. Sung, J. Ptacek, and A. M. Arvin (2012)
PNAS 109, 600-605
   Abstract »    Full Text »    PDF »
Paracrine inhibition of GM-CSF signaling by human cytomegalovirus in monocytes differentiating to dendritic cells.
J. Carlier, H. Martin, B. Mariame, B. Rauwel, C. Mengelle, H. Weclawiak, A. Coaquette, C. Vauchy, P. Rohrlich, N. Kamar, et al. (2011)
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   Abstract »    Full Text »    PDF »
Inhibition of Inflammatory Interleukin-6 Activity via Extracellular Signal-Regulated Kinase-Mitogen-Activated Protein Kinase Signaling Antagonizes Human Cytomegalovirus Reactivation from Dendritic Cells.
M. B. Reeves and T. Compton (2011)
J. Virol. 85, 12750-12758
   Abstract »    Full Text »    PDF »
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M. Dzabic, A. Rahbar, K.-C. Yaiw, M. Naghibi, P. Religa, B. Fellstrom, E. Larsson, and C. Soderberg-Naucler (2011)
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   Abstract »    Full Text »    PDF »
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L. Soroceanu, L. Matlaf, V. Bezrookove, L. Harkins, R. Martinez, M. Greene, P. Soteropoulos, and C. S. Cobbs (2011)
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K. Dziurzynski, J. Wei, W. Qiao, M. A. Hatiboglu, L.-Y. Kong, A. Wu, Y. Wang, D. Cahill, N. Levine, S. Prabhu, et al. (2011)
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