Lysophosphatidylcholine acyltransferase 1 altered phospholipid composition and regulated hepatoma progression.

Abstract:

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.

journal_name

J Hepatol

journal_title

Journal of hepatology

authors

Morita Y,Sakaguchi T,Ikegami K,Goto-Inoue N,Hayasaka T,Hang VT,Tanaka H,Harada T,Shibasaki Y,Suzuki A,Fukumoto K,Inaba K,Murakami M,Setou M,Konno H

doi

10.1016/j.jhep.2013.02.030

subject

Has Abstract

pub_date

2013-08-01 00:00:00

pages

292-9

issue

2

eissn

0168-8278

issn

1600-0641

pii

S0168-8278(13)00211-0

journal_volume

59

pub_type

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