{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T20:15:43Z","timestamp":1790712943713,"version":"4.1.0"},"reference-count":42,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2015,8,3]],"date-time":"2015-08-03T00:00:00Z","timestamp":1438560000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2015,10]]},"abstract":"Abstract<\/jats:title>\n \n Non\u2010keratinizing nasopharyngeal carcinoma (\n NPC<\/jats:styled-content>\n ) is closely associated with Epstein\u2013Barr virus (\n EBV<\/jats:styled-content>\n ) infection. The\n EBV<\/jats:styled-content>\n \u2010encoded latent membrane protein 1 (\n LMP1<\/jats:styled-content>\n ) is believed to play an important role in\n NPC<\/jats:styled-content>\n pathogenesis by virtue of its ability to activate multiple cell signalling pathways which collectively promote cell proliferation, transformation, angiogenesis, and invasiveness, as well as modulation of energy metabolism. In this study, we report that\n LMP1<\/jats:styled-content>\n increases cellular uptake of glucose and glutamine, enhances\n LDHA<\/jats:styled-content>\n activity and lactate production, but reduces pyruvate kinase activity and pyruvate concentrations.\n LMP1<\/jats:styled-content>\n also increases the phosphorylation of\n PKM2<\/jats:styled-content>\n ,\n LDHA<\/jats:styled-content>\n , and\n FGFR1<\/jats:styled-content>\n , as well as the expression of\n PDHK1<\/jats:styled-content>\n ,\n FGFR1<\/jats:styled-content>\n , c\u2010Myc, and\n HIF<\/jats:styled-content>\n \u20101\u03b1, regardless of oxygen availability. Collectively, these findings suggest that\n LMP1<\/jats:styled-content>\n promotes aerobic glycolysis. With respect to\n FGFR1<\/jats:styled-content>\n signalling,\n LMP1<\/jats:styled-content>\n not only increases\n FGFR1<\/jats:styled-content>\n expression, but also up\u2010regulates\n FGF2<\/jats:styled-content>\n , leading to constitutive activation of the\n FGFR1<\/jats:styled-content>\n signalling pathway. Furthermore, two inhibitors of\n FGFR1<\/jats:styled-content>\n (\n PD161570<\/jats:styled-content>\n and\n SU5402<\/jats:styled-content>\n ) attenuate\n LMP1<\/jats:styled-content>\n \u2010mediated aerobic glycolysis, cellular transformation (proliferation and anchorage\u2010independent growth), cell migration, and invasion in nasopharyngeal epithelial cells, identifying\n FGFR1<\/jats:styled-content>\n signalling as a key pathway in\n LMP1<\/jats:styled-content>\n \u2010mediated growth transformation. Immunohistochemical staining revealed that high levels of phosphorylated\n FGFR1<\/jats:styled-content>\n are common in primary\n NPC<\/jats:styled-content>\n specimens and that this correlated with the expression of\n LMP1<\/jats:styled-content>\n . In addition,\n FGFR1<\/jats:styled-content>\n inhibitors suppress cell proliferation and anchorage\u2010independent growth of\n NPC<\/jats:styled-content>\n cells. Our current findings demonstrate that\n LMP1<\/jats:styled-content>\n \u2010mediated\n FGFR1<\/jats:styled-content>\n activation contributes to aerobic glycolysis and transformation of epithelial cells, thereby implicating\n FGF2<\/jats:styled-content>\n \/\n FGFR1<\/jats:styled-content>\n signalling activation in the\n EBV<\/jats:styled-content>\n \u2010driven pathogenesis of\n NPC<\/jats:styled-content>\n . Copyright \u00a9 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.\n <\/jats:p>","DOI":"10.1002\/path.4575","type":"journal-article","created":{"date-parts":[[2015,6,19]],"date-time":"2015-06-19T21:20:48Z","timestamp":1434748848000},"page":"238-248","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":112,"title":["Activation of the\n FGFR1<\/scp>\n signalling pathway by the Epstein\u2013Barr virus\u2010encoded\n LMP1<\/scp>\n promotes aerobic glycolysis and transformation of human nasopharyngeal epithelial cells"],"prefix":"10.1002","volume":"237","author":[{"given":"Angela Kwok\u2010Fung","family":"Lo","sequence":"first","affiliation":[{"name":"Department of Anatomical and Cellular Pathology, State Key Laboratory in Oncology in South China and Li Ka Shing Institute of Health Science Prince of Wales Hospital, The Chinese University of Hong Kong Hong Kong"},{"name":"Cancer Research UK Cancer Centre, School of Cancer Sciences University of Birmingham Vincent 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