Abstract
Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) is one of the most common human cancers in South-East Asia exhibiting typical features of lipid accumulation. EBV-encoded latent membrane protein 2A (LMP2A) is expressed in most NPCs enhancing migration and invasion. We recently showed an increased accumulation of lipid droplets in NPC, compared with normal nasopharyngeal epithelium. It is important to uncover the mechanism behind this lipid metabolic shift to better understand the pathogenesis of NPC and provide potential therapeutic targets. We show that LMP2A increased lipid accumulation in NPC cells. LMP2A could block lipid degradation by downregulating the lipolytic gene adipose triglycerol lipase (ATGL). This is in contrast to lipid accumulation due to enhanced lipid biosynthesis seen in many cancers. Suppression of ATGL resulted in enhanced migration in vitro, and ATGL was found downregulated in NPC biopsies. The reduced expression level of ATGL correlated with poor overall survival in NPC patients. Our findings reveal a new role of LMP2A in lipid metabolism, correlating with NPC patient survival depending on ATGL downregulation.
Keywords:
EBV; adipose triglycerol lipase; latent membrane protein 2A; lipid metabolism; migration; nasopharyngeal carcinoma.