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SYK interaction with ITGβ4 suppressed by Epstein-Barr virus LMP2A modulates migration and invasion of nasopharyngeal carcinoma cells

Oncogene volume 34, pages 4491–4499 (2015)Cite this article

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Abstract

Epstein-Barr virus (EBV)-encoded Latent Membrane Protein 2A (LMP2A) is an EBV latency-associated protein regularly expressed in nasopharyngeal carcinoma (NPC). In B cells, LMP2A activity resembles that of a constitutively activated antigen receptor, which recruits the Syk tyrosine kinase to activate a set of downstream signaling pathways. LMP2A also downregulates cellular Syk levels. In the present study, we demonstrate that Syk interacts with the integrin β4 subunit (ITGβ4) of integrin α6β4 in epithelial cells and that concurrent LMP2A expression interferes with this interaction by competitive binding to Syk. We find that both Syk and LMP2A have an effect on ITGβ4 cell surface expression. However, in LMP2A expressing cells, ITGβ4 remains concentrated at the cellular protrusions, an expression pattern characteristic of motile cells, including NPC-derived epithelial cells. This effect of LMP2A on ITGβ4 localization is associated with a greater propensity for migration and invasion in-vitro, and may contribute to the invasive property of LMP2A-expressing NPC.

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Acknowledgements

This work was supported by the Swedish Cancer Society, the Swedish Research Council,Karolinska Institutet Research funds and by the Maths O Sundqvist family foundation; National Key Basic Research Program of China (2012CB526607) and Guangxi Natural Science Foundation (2013GXNSFGA019002). We thank Gösta Winberg for valuable comments to the manuscript.

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Author notes

  1. X Zhou, L Matskova and L-S Z Rathje: Shared first authorship.

  2. T Pawson and F Chen: Deceased 2013; 2011

Authors and Affiliations

  1. Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden

    X Zhou, L Matskova, L-S Z Rathje, X Xiao, M Werner, I Ignatyev, F Chen & I Ernberg

  2. Department of Otolaryngology-Head & Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, China

    X Zhou, X Xiao, N Yu, W Zhao, F Tian, B Hou & Z Zhang

  3. Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada

    G Gish & T Pawson

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Zhou, X., Matskova, L., Rathje, LS. et al. SYK interaction with ITGβ4 suppressed by Epstein-Barr virus LMP2A modulates migration and invasion of nasopharyngeal carcinoma cells. Oncogene 34, 4491–4499 (2015). https://doi.org/10.1038/onc.2014.380

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