title: Lysophosphatidylcholine acyltransferase 1 altered phospholipid composition and regulated hepatoma progression.
abstract: OBJECTIVE
  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.
authors.affiliation: Second Department of Surgery, Hamamatsu University School of Medicine, Japan.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Morita
authors.forename: Takanori
authors.initials: T
authors.lastname: Sakaguchi
authors.forename: Koji
authors.initials: K
authors.lastname: Ikegami
authors.forename: Naoko
authors.initials: N
authors.lastname: Goto-Inoue
authors.forename: Takahiro
authors.initials: T
authors.lastname: Hayasaka
authors.forename: Vu Thi
authors.initials: VT
authors.lastname: Hang
authors.forename: Hiroki
authors.initials: H
authors.lastname: Tanaka
authors.forename: Takashi
authors.initials: T
authors.lastname: Harada
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Shibasaki
authors.forename: Atsushi
authors.initials: A
authors.lastname: Suzuki
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Fukumoto
authors.forename: Keisuke
authors.initials: K
authors.lastname: Inaba
authors.forename: Makoto
authors.initials: M
authors.lastname: Murakami
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Setou
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Konno
mesh_terms: D008243:1-Acylglycerophosphocholine O-Acyltransferase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D018450:Disease Progression; D005260:Female; D055785:Gene Knockdown Techniques; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity; D015854:Up-Regulation
chemical_list: D010743:Phospholipids; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D008243:1-Acylglycerophosphocholine O-Acyltransferase; C526202:Lpcat1 protein, human
keywords: Ca(2+)-independent phospholipase A(2)β; Cancer lipidomics; DPPC; HCC; Hepatocellular carcinoma; IMS; Imaging mass spectrometry; LPC; LPCAT; LPCAT1; MALDI; NAFLD; PAF; PC; PCA; cPLA(2)α; cytosolic phospholipase A(2)α; dipalmitoyl phosphatidylcholine; hepatocellular carcinoma; iPLA(2)β; imaging mass spectrometry; lysophosphatidylcholine; lysophosphatidylcholine acyltransferase; matrix-assisted laser desorption/ionization; non-alcoholic fatty liver disease; phosphatidylcholine; platelet activating factor; principal component analysis