Downregulation of adipose triglyceride lipase by EB viral-encoded LMP2A links lipid accumulation to increased migration in nasopharyngeal carcinoma.
Downregulation of adipose triglyceride lipase by EB viral-encoded LMP2A links lipid accumulation to increased migration in nasopharyngeal carcinoma.
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DOI：
10.1002/1878-0261.12824
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发表时间：
2020-12
影响因子：
6.6
通讯作者：
Ernberg I
中科院分区：
文献类型：
--
作者：
Zheng S;Matskova L;Zhou X;Xiao X;Huang G;Zhang Z;Ernberg I
EB病毒（EBV）相关的鼻咽癌（NPC）细胞显示出明显的脂质积聚。在这里，我们发现EBV编码的膜蛋白2A（LMP2A）通过抑制脂解基因脂肪细胞三酰甘油脂肪酶（ATGL）诱导NPC细胞中的脂质积累。ATGL的抑制导致NPC细胞中脂质积聚和迁移能力增强。NPC细胞中ATGL的缺失与较差的总体存活率相关。 EB病毒（EBV）相关鼻咽癌（NPC）是东南亚最常见的人类癌症之一，表现出典型的脂质蓄积特征。EBV编码的潜伏膜蛋白2A（LMP2A）在大多数NPC中表达，增强迁移和侵袭。我们最近发现，与正常鼻咽上皮相比，NPC中的脂滴积聚增加。揭示这种脂质代谢变化的机制对于更好地理解NPC的发病机制和提供潜在的治疗靶点具有重要意义。我们发现LMP2A增加了NPC细胞中的脂质积累。LMP2A可通过下调脂肪分解基因脂肪三甘油脂肪酶（ATGL）的表达而阻断脂质降解。这与在许多癌症中观察到的由于增强的脂质生物合成而导致的脂质积累形成对比。ATGL的抑制导致体外迁移增强，并且发现ATGL在NPC活检中下调。ATGL表达水平的降低与NPC患者的总体生存率相关。我们的研究结果揭示了LMP2A在脂质代谢中的新作用，其与依赖于ATGL下调的NPC患者生存相关。
Epstein–Barr virus (EBV)‐associated nasopharyngeal carcinoma (NPC) cells display conspicuous lipid accumulation. Here, we show that EBV‐encoded membrane protein 2A (LMP2A) induces lipid accumulation in NPC cells by inhibition of lipolytic gene, adipocyte triacylglycerol lipase (ATGL). Inhibition of ATGL results in enhanced lipid accumulation and migratory capacity in NPC cells. Loss of ATGL in NPC cells correlates with poor overall survival. 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.
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影响因子：
82.9
作者：
通讯作者：
--
影响因子：
8
作者：
Di Leo L;Vegliante R;Ciccarone F;Salvatori I;Scimeca M;Bonanno E;Sagnotta A;Grazi GL;Aquilano K;Ciriolo MR
通讯作者：
Ciriolo MR
DOI：
10.1007/s12032-014-0391-z
发表时间：
2015-01
期刊：
Medical oncology (Northwood, London, England)
影响因子：
--
作者：
Cai Y;Wang J;Zhang L;Wu D;Yu D;Tian X;Liu J;Jiang X;Shen Y;Zhang L;Ren M;Huang P
通讯作者：
Huang P
影响因子：
6.7
作者：
Kong QL;Hu LJ;Cao JY;Huang YJ;Xu LH;Liang Y;Xiong D;Guan S;Guo BH;Mai HQ;Chen QY;Zhang X;Li MZ;Shao JY;Qian CN;Xia YF;Song LB;Zeng YX;Zeng MS
通讯作者：
Zeng MS
Epstein-Barr病毒编码的LMP2A通过EGFR/Ca(2)/钙蛋白酶/ITGbeta4轴刺激鼻咽癌细胞的迁移。
影响因子：
2.4
作者：
Liang J;Zheng S;Xiao X;Wei J;Zhang Z;Ernberg I;Matskova L;Huang G;Zhou X
通讯作者：
Zhou X