Skip to main content
Article thumbnail
Location of Repository

Phospholipase PLA2G7, associated with aggressive prostate cancer, promotes prostate cancer cell migration and invasion and is inhibited by statins

By Paula Vainio, Laura Lehtinen, Tuomas Mirtti, Mika Hilvo, Tuulikki Seppänen-Laakso, Johannes Virtanen, Anna Sankila, Stig Nordling, Johan Lundin, Antti Rannikko, Matej Orešič, Olli Kallioniemi and Kristiina Iljin


Prostate cancer is the second leading cause of cancer mortality in men in developed countries. Due to the heterogeneous nature of the disease, design of novel personalized treatments is required to achieve efficient therapeutic responses. We have recently identified phospholipase 2 group VII (PLA2G7) as a potential drug target especially in ERG oncogene positive prostate cancers. Here, the expression profile of PLA2G7 was studied in 1137 prostate cancer and 409 adjacent non-malignant prostate tissues using immunohistochemistry to validate its biomarker potential and putative association with disease progression. In order to reveal the molecular alterations induced by PLA2G7 impairment, lipidomic and gene expression profiling was performed in response to PLA2G7 silencing in cultured prostate cancer cells. Moreover, the antineoplastic effect of statins combined with PLA2G7 impairment was studied in prostate cancer cells to evaluate the potential of repositioning of in vivo compatible drugs developed for other indications towards anti-cancer purposes. The results indicated that PLA2G7 is a cancer-selective biomarker in 50% of prostate cancers and associates with aggressive disease. The alterations induced by PLA2G7 silencing highlighted the potential of PLA2G7 inhibition as an anti-proliferative, pro-apoptotic and anti-migratorial therapeutic approach in prostate cancer. Moreover, the anti-proliferative effect of PLA2G7 silencing was potentiated by lipid-lowering statins in prostate cancer cells. Taken together, our results support the potential of PLA2G7 as a biomarker and a drug target in prostate cancer and present a rationale for combining PLA2G7 inhibition with the use of statins in prostate cancer management

Topics: Research Papers
Publisher: Impact Journals LLC
OAI identifier:
Provided by: PubMed Central
Download PDF:
Sorry, we are unable to provide the full text but you may find it at the following location(s):
  • http://www.pubmedcentral.nih.g... (external link)
  • Suggested articles


    1. (2010). A comprehensive panel of three-dimensional models for studies of prostate cancer growth, invasion and drug responses. PLoS One.
    2. (2011). ALDH activity indicates increased tumorigenic cells, but not cancer stem cells, in prostate cancer cell lines. In Vivo.
    3. (2010). ALDH1A1 is a marker for malignant prostate stem cells and predictor of prostate cancer patients’ outcome. Lab Invest.
    4. (2011). Arachidonic acid pathway members PLA2G7, HPGD, EPHX2, and CYP4F8 identifi ed as putative novel therapeutic targets in prostate cancer.
    5. (2010). Autotaxin promotes cancer invasion via the lysophosphatidic acid receptor 4: participation of the cyclic AMP/EPAC/Rac1 signaling pathway in invadopodia formation. Cancer Res.
    6. (2004). Bioconductor: open software development for computational biology and bioinformatics. Genome Biol.
    7. (2009). Biology of platelet-activating factor acetylhydrolase (PAF-AH, lipoprotein associated phospholipase A2). Cardiovasc Drugs Ther.
    8. (2009). Castellino FJ, Schorey JS, D’Souza-Schorey C. ADP-ribosylation factor 6 regulates tumorigenic and invasive properties in vivo. Cancer Res.
    9. (2010). Dietary n-3 polyunsaturated fatty acids fail to reduce prostate tumorigenesis in the PB-ErbB-2 x Pten(+/-) preclinical mouse model. Cell Cycle.
    10. (2005). Effects of atorvastatin versus other statins on fasting and postprandial C-reactive protein and lipoprotein-associated phospholipase A2 in patients with coronary heart disease versus control subjects.
    11. (2008). Effects of the direct lipoprotein-associated phospholipase A(2) inhibitor darapladib on human coronary atherosclerotic plaque. Circulation.
    12. (2009). ETS family transcription factors collaborate with alternative signaling pathways to induce carcinoma Oncotarget 2011; 2: 1176 - 1190 1189 from adult murine prostate cells.
    13. (1998). Expression of plasma platelet-activating factor acetylhydrolase is transcriptionally regulated by mediators of infl ammation.
    14. (2010). FZD4 as a mediator of ERG oncogene-induced WNT signaling and epithelial-to-mesenchymal transition in human prostate cancer cells. Cancer Res.
    15. (2011). Global cancer statistics.
    16. (2010). High aldehyde dehydrogenase activity identifi es tumorinitiating and metastasis-initiating cells in human prostate cancer. Cancer Res.
    17. (2010). identifi ed from a zebrafi sh chemical genetic screen for antiangiogenic compounds, suppresses the growth of prostate cancer. Eur Urol.
    18. (2011). Improved biochemical outcomes with statin use in patients with high-risk localized prostate cancer treated with radiotherapy. Int J Radiat Oncol Biol Phys.
    19. (1998). Induction by lysophosphatidylcholine, a major phospholipid component of atherogenic lipoproteins, of human coronary artery smooth muscle cell migration. Circulation.
    20. (2008). Inhibition of lipoproteinassociated phospholipase A2 reduces complex coronary atherosclerotic plaque development. Nat Med.
    21. (2004). Linear models and empirical bayes methods for assessing differential expression in microarray experiments. Stat Appl Genet Mol Biol.
    22. (2006). Lipoprotein-associated phospholipase A2 independently predicts the angiographic diagnosis of coronary artery disease and coronary death. Am Heart J.
    23. (2005). Lipoproteinassociated phospholipase A2 activity is associated with risk of coronary heart disease and ischemic stroke: the Rotterdam Study. Circulation.
    24. (2006). Lipoproteinassociated phospholipase A2 and its association with cardiovascular outcomes in patients with acute coronary syndromes
    25. (2000). Lipoproteinassociated phospholipase A2 as an independent predictor of coronary heart disease.
    26. (2009). Lysophospholipids stimulate prostate cancer cell migration via TRPV2 channel activation. Biochim Biophys Acta.
    27. Modulation of melanoma cell phospholipid metabolism in response to heat shock protein 90 inhibition.
    28. (2010). Prostate cancer Oncotarget 2011; 2: 1176 - 1190 1190 and PSA among statin users in the Finnish prostate cancer screening trial.
    29. (2005). Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer.
    30. (2005). Role of lipoprotein-associated phospholipase A2 in atherosclerosis: biology, epidemiology, and possible therapeutic target. Arterioscler. Thromb Vasc Biol.
    31. (2008). Role of the TMPRSS2-ERG gene fusion in prostate cancer.
    32. (2008). Stat3 promotes metastatic progression of prostate cancer.
    33. (2006). Statin drugs and risk of advanced prostate cancer.
    34. (2008). Statin induces apoptosis and cell growth arrest in prostate cancer cells. Cancer Epidemiol Biomarkers Prev.
    35. (2010). Statin use and risk of prostate cancer recurrence in men treated with radiation therapy. J Clin Oncol.
    36. (2011). Statins reduce the androgen sensitivity and cell proliferation by decreasing the androgen receptor protein in prostate cancer cells. Prostate.
    37. (2008). Synergistic response to oncogenic mutations defi nes gene class critical to cancer phenotype.
    38. (1993). The phospholipase-A2 reaction leads to increased monocyte adhesion of endothelial cells via the expression of adhesion molecules.
    39. The Siah2-HIF-FoxA2 axis in prostate cancer – new markers and therapeutic opportunities.
    40. (2009). Thiazolidinediones regulate expression of cell cycle proteins in human prostate cancer cells via PPARgammadependent and PPARgamma-independent pathways. Cell Cycle.
    41. (2006). TMPRSS2 fusions with oncogenic ETS factors in prostate cancer involve unbalanced genomic rearrangements and are associated with HDAC1 and epigenetic reprogramming. Cancer Res.
    42. (2008). TMPRSS2-ERG fusion, a common genomic alteration in prostate cancer activates C-MYC and abrogates prostate epithelial differentiation. Oncogene.
    43. (2006). TMPRSS2:ERG fusion by translocation or interstitial deletion is highly relevant in androgen-dependent prostate cancer, but is bypassed in late-stage androgen receptor-negative prostate cancer. Cancer Res.
    44. (2010). Utility of Lp-PLA2 in LipidLowering Therapy.

    To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.