Enhanced aerobic glycolysis of nasopharyngeal carcinoma cells by Epstein-Barr virus latent membrane protein 1.
Exp Cell Res
; 359(1): 94-100, 2017 10 01.
Article
em En
| MEDLINE
| ID: mdl-28827059
ABSTRACT
Latent membrane protein 1 (LMP1) is a principal viral oncoprotein in Epstein-Barr virus (EBV)-associated malignancies, including nasopharyngeal carcinoma (NPC), which acts through regulating tumorigenesis and metabolic reprogramming of cancers. In the presence of oxygen, we demonstrated that glucose consumption, lactate production and lactate dehydrogenase (LDH) activity were significantly increased upon LMP1 expression in NPC cells and in a LMP1 variant derived from NPC patients-transformed BALB/c-3T3 cells. The amounts of the α subunit of hypoxia-inducible factor-1 (HIF-1α), a key regulator of aerobic glycolysis, and its targets, pyruvate dehydrogenase kinase 1 (PDK1) and the pyruvate kinase M2 (PKM2) isoform, were also consistently elevated by LMP1. Moreover, in parallel with reductions in the oxygen consumption rate and mitochondrial membrane potential in cells, an augmented extracellular lactate concentration was observed due to LMP1 induction. In conclusion, our results proved facilitation of the Warburg effect by LMP1 through alteration of mitochondrial function in NPC cells.
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Base de dados:
MEDLINE
Assunto principal:
Carcinoma
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Proteínas da Matriz Viral
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Neoplasias Nasofaríngeas
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article