Downregulation of adipose triglyceride lipase by EB viral-encoded LMP2A links lipid accumulation to increased migration in nasopharyngeal carcinoma.
Cell Line, Tumor
Cell Movement
Down-Regulation
Gene Expression Regulation, Neoplastic
Glucose
/ metabolism
Herpesvirus 4, Human
/ metabolism
Humans
Lipase
/ metabolism
Lipid Metabolism
/ genetics
Lipids
/ chemistry
Nasopharyngeal Neoplasms
/ genetics
Survival Analysis
Viral Matrix Proteins
/ metabolism
EBV
adipose triglycerol lipase
latent membrane protein 2A
lipid metabolism
migration
nasopharyngeal carcinoma
Journal
Molecular oncology
ISSN: 1878-0261
Titre abrégé: Mol Oncol
Pays: United States
ID NLM: 101308230
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
received:
01
11
2019
revised:
02
07
2020
accepted:
12
10
2020
pubmed:
17
10
2020
medline:
4
9
2021
entrez:
16
10
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33064888
doi: 10.1002/1878-0261.12824
pmc: PMC7718958
doi:
Substances chimiques
EBV-associated membrane antigen, Epstein-Barr virus
0
Lipids
0
Viral Matrix Proteins
0
Lipase
EC 3.1.1.3
PNPLA2 protein, human
EC 3.1.1.3
Glucose
IY9XDZ35W2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3234-3252Informations de copyright
© 2020 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.
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