Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV) infection related head and neck malignancy with obvious regional aggregation and racial susceptibility. Previously, we have identified that EBV encoded latent membrane protein LMP2A decreases the expression of adipose triglyceride lipase (ATGL), as the first key rate-limiting enzyme of triglyceride (TG) hydrolysis, resulting in lipid droplets (LDs) accumulation and accelerating the motility of NPC cells. Here, we proved that the mRNA and protein expression of ATGL is downregulated in NPC. Ectopic overexpression of ATGL inhibits the proliferation, colony formation ability in vitro and suppressed their tumorigenesis in vivo. Mean while, ATGL contributes to the apoptosis induction through  mitochondrial pathway and metastasis suppression by reversing epithelial-mesenchymal transition (EMT). In addition, higher level of ATGL increases the sensitivity of NPC cells to cisplatin treatment. As a LDs regulator, we found that ATGL overexpression reprogrammed the lipid metabolism by transcriptomic and lipidomics analysis. The LDs accumulation is positively correlated with growth and movement of NPC. Interestingly, LDs might function as a inflammation reservoir in NPC cells. We observed that overexpressing ATGL suppresses the expression of inflammatory factors, including IL6, IL8, CXCL2 and IL1? by activating PPAR-? signaling pathway, despite the NF-?B (p65) was activated as well. In summary, ATGL act as as tumor suppressor gene in NPC, and it modulates LDs accumulation and the subsequently inflammatory reaction. Our data might shed light to a novel pathogenesis of NPC, and provide a new therapeutic target for NPC from the aspect of lipid metabolism.

Keywords: nasopharyngeal carcinoma, lipid droplets, NF-?B/PPAR? signaling pathway, inflammatory response.