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.
journal_name
Oncogenejournal_title
Oncogeneauthors
Zhou X,Matskova L,Rathje LS,Xiao X,Gish G,Werner M,Ignatyev I,Yu N,Zhao W,Tian F,Hou B,Zhang Z,Pawson T,Chen F,Ernberg Idoi
10.1038/onc.2014.380subject
Has Abstractpub_date
2015-08-20 00:00:00pages
4491-9issue
34eissn
0950-9232issn
1476-5594pii
onc2014380journal_volume
34pub_type
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