Lysophosphatidylcholine acyltransferase 1 (LPCAT1) overexpression in human colorectal cancer
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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 [14C]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.
KeywordsColorectal cancer Lysophosphatidic acyltransferase Microarrays Lipid metabolism Phosphatidylcholine
We are grateful to Pamela Celis, Susanne Bruun, Lisbeth Kjeldsen, and Jette Jensen for their excellent technical assistance as well as to Jeppe Praetorius, Institute of Anatomy, University of Aarhus, for confocal microscopy and Ludwig Wagner, Dept. of Medicine III, University of Vienna who kindly provided us with the GST-secretagogin construct. The work was supported by grants from the John and Birthe Meyer Foundation, the Novo Nordisk foundation, Toyota Fonden Denmark, the US National Institutes of Health (DK56598, DK59935, HL081554, and P30-DK56350), the Danish Research Council, the University and County of Aarhus, the Nordic Cancer Union, The Mads Clausen Foundation, and the Karen Elise Jensen foundation.
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