Lysophosphatidylcholine acyltransferase 1 (LPCAT1) overexpression in human colorectal cancer.
The alteration of the choline metabolite profile is a well-established characteristic of cancer cells. In colorectal cancer (CRC), phosphatidylcholine is the most prominent phospholipid. In the present study, we report that lysophosphatidylcholine acyltransferase 1 (LPCAT1; NM_024830.3), the enzyme that converts lysophosphatidylcholine into phosphatidylcholine, was highly overexpressed in colorectal adenocarcinomas when compared to normal mucosas. Our microarray transcription profiling study showed a significant (p < 10(-8)) transcript overexpression in 168 colorectal adenocarcinomas when compared to ten normal mucosas. Immunohistochemical analysis of colon tumors with a polyclonal antibody to LPCAT1 confirmed the upregulation of the LPCAT1 protein. Overexpression of LPCAT1 in COS7 cells localized the protein to the endoplasmic reticulum and the mitochondria and increased LPCAT1 specific activity 38-fold. In cultured cells, overexpressed LPCAT1 enhanced the incorporation of [(14)C]palmitate into phosphatidylcholine. COS7 cells transfected with LPCAT1 showed no growth rate alteration, in contrast to the colon cancer cell line SW480, which significantly (p < 10(-5)) increased its growth rate by 17%. We conclude that LPCAT1 may contribute to total choline metabolite accumulation via phosphatidylcholine remodeling, thereby altering the CRC lipid profile, a characteristic of malignancy.
Mansilla
Francisco
F
Molecular Diagnostic Laboratory, Center for Molecular Clinical Cancer Research, Arhus University Hospital/Skejby, 8200, Aarhus, Denmark. Francisco.mansilla@ki.au.dk
da Costa
Kerry-Ann
KA
Wang
Shuli
S
Kruhøffer
Mogens
M
Lewin
Tal M
TM
Orntoft
Torben F
TF
Coleman
Rosalind A
RA
Birkenkamp-Demtröder
Karin
K
D008243:1-Acylglycerophosphocholine O-Acyltransferase / Q000096:biosynthesis*; D000230:Adenocarcinoma / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000818:Animals; D019556:COS Cells; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D002794:Choline / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D020411:Oligonucleotide Array Sequence Analysis
D009363:Neoplasm Proteins; D008243:1-Acylglycerophosphocholine O-Acyltransferase; C526202:Lpcat1 protein, human; D002794:Choline