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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.

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endoplasmic reticulum






colorectal cancer


microsatellite stable


microsatellite unstable


  1. Stewart BW, Kleihues P (2003) World Cancer report. ISBN 92 832 0411 5. World Health Organization WHO Press. Ref Type: Report

  2. Birkenkamp-Demtroder K, Christensen LL, Olesen SH, Frederiksen CM, Laiho P, Aaltonen LA, Laurberg S, Sorensen FB, Hagemann R, ORntoft TF (2002) Gene expression in colorectal cancer. Cancer Res 62:4352–4363

    PubMed  CAS  Google Scholar 

  3. Nakanishi H, Shindou H, Hishikawa D, Harayama T, Ogasawara R, Suwabe A, Taguchi R, Shimizu T (2006) Cloning and characterization of mouse lung-type acyl-CoA:lysophosphatidylcholine acyltransferase 1 (LPCAT1). Expression in alveolar type II cells and possible involvement in surfactant production. J Biol Chem 281:20140–20147

    Article  PubMed  CAS  Google Scholar 

  4. Chen X, Hyatt BA, Mucenski ML, Mason RJ, Shannon JM (2006) Identification and characterization of a lysophosphatidylcholine acyltransferase in alveolar type II cells. Proc Natl Acad Sci U S A 103:11724–11729

    Article  PubMed  CAS  Google Scholar 

  5. Agarwal AK, Sukumaran S, Bartz R, Barnes RI, Garg A (2007) Functional characterization of human 1-acylglycerol-3-phosphate-O-acyltransferase isoform 9: cloning, tissue distribution, gene structure, and enzymatic activity. J Endocrinol 193:445–457

    Article  PubMed  CAS  Google Scholar 

  6. Bishop WR, Bell RM (1988) Assembly of phospholipids into cellular membranes: biosynthesis, transmembrane movement and intracellular translocation. Annu Rev Cell Biol 4:579–610

    Article  PubMed  CAS  Google Scholar 

  7. White DA (1973) The phospholipids composition of mammalian tissues. In: Ansell GB, Hawthorne JN, Dawson RMC (eds) Form and function of phospholipids. Elsevier, Amsterdam, pp 441–482

    Google Scholar 

  8. Dueck DA, Chan M, Tran K, Wong JT, Jay FT, Littman C, Stimpson R, Choy PC (1996) The modulation of choline phosphoglyceride metabolism in human colon cancer. Mol Cell Biochem 20(162):97–103

    Google Scholar 

  9. Dobrzynska I, Szachowicz-Petelska B, Sulkowski S, Figaszewski Z (2005) Changes in electric charge and phospholipids composition in human colorectal cancer cells. Mol Cell Biochem 276:113–119

    Article  PubMed  CAS  Google Scholar 

  10. Preetha A, Banerjee R, Huilgol N (2005) Surface activity, lipid profiles and their implications in cervical cancer. J Cancer Res Ther 1:180–186

    Article  PubMed  CAS  Google Scholar 

  11. Mansilla F, Birkenkamp-Demtroder K, Kruhoffer M, Sorensen FB, Andersen CL, Laiho P, Aaltonen LA, Verspaget HW, ORntoft TF (2007) Differential expression of DHHC9 in microsatellite stable and instable human colorectal cancer subgroups. Br J Cancer 96:1896–1903

    Article  PubMed  CAS  Google Scholar 

  12. Olesen SH, Christensen LL, Sorensen FB, Cabezon T, Laurberg S, ORntoft TF, Birkenkamp-Demtroder K (2005) Human FK506 binding protein 65 is associated with colorectal cancer. Mol Cell Proteomics 4:534–544

    Article  PubMed  CAS  Google Scholar 

  13. Bligh EG, Dyer WJ (1959) A rapid method of total lipid extraction and purification. Can J Biochem Physiol 37:911–917

    PubMed  CAS  Google Scholar 

  14. Koc H, Mar MH, Ranasinghe A, Swenberg JA, Zeisel SH (2002) Quantitation of choline and its metabolites in tissues and foods by liquid chromatography/electrospray ionization-isotope dilution mass spectrometry. Anal Chem 74:4734–4740

    Article  PubMed  CAS  Google Scholar 

  15. Birkenkamp-Demtroder K, Olesen SH, Sorensen FB, Laurberg S, Laiho P, Aaltonen LA, ORntoft TF (2005) Differential gene expression in colon cancer of the caecum versus the sigmoid and rectosigmoid. Gut 54:374–384

    Article  PubMed  CAS  Google Scholar 

  16. Kruhoffer M, Jensen JL, Laiho P, Dyrskjot L, Salovaara R, Arango D, Birkenkamp-Demtroder K, Sorensen FB, Christensen LL, Buhl L, Mecklin JP, Jarvinen H, Thykjaer T, Wikman FP, Bech-Knudsen F, Juhola M, Nupponen NN, Laurberg S, Andersen CL, Aaltonen LA, ORntoft TF (2005) Gene expression signatures for colorectal cancer microsatellite status and HNPCC. Br J Cancer 20(92):240–2248

    Google Scholar 

  17. Lewin TM, Wang P, Coleman RA (1999) Analysis of amino acid motifs diagnostic for the sn-glycerol-3-phosphate acyltransferase reaction. Biochemistry 38:5764–5771

    Article  PubMed  CAS  Google Scholar 

  18. Gonzalez-Baro MR, Granger DA, Coleman RA (2001) Mitochondrial glycerol phosphate acyltransferase contains two transmembrane domains with the active site in the N-terminal domain facing the cytosol. J Biol Chem 276:43182–43188

    Article  PubMed  CAS  Google Scholar 

  19. Rapaport D (2003) Finding the right organelle. Targeting signals in mitochondrial outer-membrane proteins. EMBO Rep 4:948–952

    Article  PubMed  CAS  Google Scholar 

  20. Walkey CJ, Kalmar GB, Cornell RB (1994) Overexpression of rat liver CTP:phosphocholine cytidylyltransferase accelerates phosphatidylcholine synthesis and degradation. J Biol Chem 269:5742–5749

    PubMed  CAS  Google Scholar 

  21. Lykidis A, Murti KG, Jackowski S (1998) Cloning and characterization of a second human CTP:phosphocholine cytidylyltransferase. J Biol Chem 273:14022–14029

    Article  PubMed  CAS  Google Scholar 

  22. Baburina I, Jackowski S (1999) Cellular responses to excess phospholipid. J Biol Chem 274:9400–9408

    Article  PubMed  CAS  Google Scholar 

  23. Glunde K, Jie C, Bhujwalla ZM (2006) Mechanisms of indomethacin-induced alterations in the choline phospholipid metabolism of breast cancer cells. Neoplasia 8:758–771

    Article  PubMed  CAS  Google Scholar 

  24. Aboagye EO, Bhujwalla ZM (1999) Malignant transformation alters membrane choline phospholipid metabolism of human mammary epithelial cells. Cancer Res 59:80–84

    PubMed  CAS  Google Scholar 

  25. Ackerstaff E, Glunde K, Bhujwalla ZM (2003) Choline phospholipid metabolism: a target in cancer cells? J Cell Biochem 90:525–533

    Article  PubMed  CAS  Google Scholar 

  26. Vance JE, Vance DE (2004) Phospholipid biosynthesis in mammalian cells. Biochem Cell Biol 82:113–128

    Article  PubMed  CAS  Google Scholar 

  27. Nakagami K, Uchida T, Ohwada S, Koibuchi Y, Suda Y, Sekine T, Morishita Y (1999) Increased choline kinase activity and elevated phosphocholine levels in human colon cancer. Jpn J Cancer Res 90:419–424

    PubMed  CAS  Google Scholar 

  28. Ramirez de MA, Rodriguez-Gonzalez A, Gutierrez R, Martinez-Pineiro L, Sanchez J, Bonilla F, Rosell R, Lacal J (2002) Overexpression of choline kinase is a frequent feature in human tumor-derived cell lines and in lung, prostate, and colorectal human cancers. Biochem Biophys Res Commun 296:580–583

    Article  CAS  Google Scholar 

  29. Glunde K, Jie C, Bhujwalla ZM (2004) Molecular causes of the aberrant choline phospholipid metabolism in breast cancer. Cancer Res 64:4270–4276

    Article  PubMed  CAS  Google Scholar 

  30. Zeisig R, Koklic T, Wiesner B, Fichtner I, Sentjurc M (2007) Increase in fluidity in the membrane of MT3 breast cancer cells correlates with enhanced cell adhesion in vitro and increased lung metastasis in NOD/SCID mice. Arch Biochem Biophys 459:98–106

    Article  PubMed  CAS  Google Scholar 

  31. Jorgensen K, Hoyrup P, Pedersen TB, Mouritsen OG (2001) Dynamical and structural properties of lipid membranes in relation to liposomal drug delivery systems. Cell Mol Biol Lett 6:255–263

    PubMed  CAS  Google Scholar 

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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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Correspondence to Francisco Mansilla.

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Mansilla, F., da Costa, KA., Wang, S. et al. Lysophosphatidylcholine acyltransferase 1 (LPCAT1) overexpression in human colorectal cancer. J Mol Med 87, 85–97 (2009).

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