Assuntos
Apoptose/efeitos dos fármacos , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Receptores Órfãos Semelhantes a Receptor Tirosina Quinase/antagonistas & inibidores , Bibliotecas de Moléculas Pequenas/uso terapêutico , Linhagem Celular Tumoral , Humanos , Prognóstico , Transdução de Sinais/efeitos dos fármacosRESUMO
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 ß4 subunit (ITGß4) of integrin α6ß4 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 ITGß4 cell surface expression. However, in LMP2A expressing cells, ITGß4 remains concentrated at the cellular protrusions, an expression pattern characteristic of motile cells, including NPC-derived epithelial cells. This effect of LMP2A on ITGß4 localization is associated with a greater propensity for migration and invasion in-vitro, and may contribute to the invasive property of LMP2A-expressing NPC.