Lysophosphatidylcholine acyltransferase 1 altered phospholipid composition and regulated hepatoma progression
Lysophosphatidylcholine acyltransferase 1 altered phospholipid composition and regulated hepatoma progression
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DOI：
10.1016/j.jhep.2013.02.030
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发表时间：
2013-08-01
影响因子：
25.7
通讯作者：
Konno, Hiroyuki
中科院分区：
文献类型：
--
作者：
Morita, Yoshifumi;Sakaguchi, Takanori;Konno, Hiroyuki
背景与目的：几种脂质合成途径在肝细胞癌的发生发展中起着重要作用，但其确切的分子机制尚不清楚。在此，我们揭示了溶血磷脂酰基转移酶(LPCAT)调节的磷脂组成改变与肝细胞癌进展的关系。方法：采用成像质谱仪(IMS)对37例肝细胞癌切除标本进行分子脂组学筛选。RT-PCR和Western blotting检测LPCAT的mRNA和蛋白水平，LPCAT催化溶血磷脂酰胆碱(LPC)转化为磷脂酰胆碱(PC)，并对某些脂肪酸具有底物特异性。我们检测了LPCAT1的过表达或敲除对肝癌细胞系细胞增殖、迁移和侵袭的影响。结果：IMS显示，在肝癌组织中，sn-2位的棕榈油酸或油酸增加了PC物种，而sn-1-位的棕榈酸减少了LPC。负责LPC向PC转化的LPCAT1的mRNA和蛋白在肝细胞中比在周围实质中丰富。在细胞系实验中，LPCAT1过表达丰富了IMS中观察到的PC，并促进了细胞的增殖、迁移和侵袭。结论：IMS检测发现肝细胞癌组织中存在某些特定PC的富含或缺失。肝细胞癌中磷脂成分的改变会影响肿瘤的性质。LPCAT1调节磷脂组成，为肝癌细胞创造有利条件。LPCAT1是抑制肝细胞癌进展的有效靶向分子。(C)2013年欧洲肝脏研究协会。爱思唯尔出版，版权所有。
Background & Aims: Several lipid synthesis pathways play important roles in the development and progression of hepatocellular carcinoma (HCC), although the precise molecular mechanisms remain to be elucidated. Here, we show the relationship between HCC progression and alteration of phospholipid composition regulated by lysophosphatidylcholine acyltransferase (LPCAT).Methods: Molecular lipidomic screening was performed by imaging mass spectrometry (IMS) in 37 resected HCC specimens. RT-PCR and Western blotting were carried out to examine the mRNA and protein levels of LPCATs, which catalyze the conversion of lysophosphatidylcholine (LPC) into phosphatidylcholine (PC) and have substrate specificity for some kinds of fatty acids. We examined the effect of LPCAT1 overexpression or knockdown on cell proliferation, migration, and invasion in HCC cell lines.Results: IMS revealed the increase of PC species with palmitoleic acid or oleic acid at the sn-2-position and the reduction of LPC with palmitic acid at the sn-1-position in HCC tissues. mRNA and protein of LPCAT1, responsible for LPC to PC conversion, were more abundant in HCCs than in the surrounding parenchyma. In cell line experiments, LPCAT1 overexpression enriched PCs observed in IMS and promoted cell proliferation, migration, and invasion. LPCAT1 knockdown did viceversa.Conclusions: Enrichment or depletion of some specific PCs, was found in HCC by IMS. Alteration of phospholipid composition in HCC would affect tumor character. LPCAT1 modulates phospholipid composition to create favorable conditions to HCC cells. LPCAT1 is a potent target molecule to inhibit HCC progression. (C) 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.