Activation of the FGFR1 signalling pathway by the Epstein-Barr virus-encoded LMP1 promotes aerobic glycolysis and transformation of human nasopharyngeal epithelial cells.

摘要: Non-keratinizing nasopharyngeal carcinoma (NPC) is closely associated with Epstein-Barr virus (EBV) infection. The EBV-encoded latent membrane protein 1 (LMP1) believed to play an important role in NPC pathogenesis by virtue of its ability activate multiple cell signalling pathways which collectively promote proliferation, transformation, angiogenesis, and invasiveness, as well modulation energy metabolism. In this study, we report that LMP1 increases cellular uptake glucose glutamine, enhances LDHA activity lactate production, but reduces pyruvate kinase concentrations. also the phosphorylation PKM2, LDHA, FGFR1, expression PDHK1, c-Myc, HIF-1α, regardless oxygen availability. Collectively, these findings suggest promotes aerobic glycolysis. With respect FGFR1 signalling, not only expression, up-regulates FGF2, leading constitutive activation pathway. Furthermore, two inhibitors (PD161570 SU5402) attenuate LMP1-mediated glycolysis, transformation (proliferation anchorage-independent growth), migration, invasion epithelial cells, identifying a key pathway growth transformation. Immunohistochemical staining revealed high levels phosphorylated are common primary specimens correlated LMP1. addition, suppress proliferation cells. Our current demonstrate contributes glycolysis thereby implicating FGF2/FGFR1 EBV-driven NPC.