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

Abstract

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.

Tuberous Sclerosis Complex 2 Loss Increases Lysophosphatidylcholine Synthesis in Lymphangioleiomyomatosis

“…PLA2 hydrolyzes phosphatidylcholine (PC), releasing LPC and arachidonic acid, which can be further metabolized to synthesize eicosanoids. PLA2 isoforms have been shown to play roles in lung injury, cancer, inflammation, and angiogenesis through the production of bioactive lipids (14)(15)(16)(17)(18)(19). The PLA2 superfamily of lipolytic enzymes comprises 16 groups and at least 22 isoforms, which are classified based on their cellular localization (cytosolic and secretory) and chemical properties (calcium dependent and calcium independent).…”

Downregulation of sorting nexin 10 is associated with overexpression of miR-30d during liver cancer progression in rats

“…This pattern is indicative of elevated transcriptional levels and synthesis of proteins participating in cancer progression. This pattern was detected for all of the genes analyzed [8][9][10][11][12] with the exception of SNX10, which showed an inverse correlation between protein and gene expression.…”

“…With the exception of SNX10, some information is available in the literature regarding the participation of the other five genes in cancer progression. [7][8][9][10][11] The limited information related to the SNX10 protein and its relationship with cancer, together with the notable increase in SNX10 gene expression, prompted us to analyze the SNX10 protein via western blotting.…”

Blood mRNA Expression Profiling Predicts Survival in Patients Treated with Tremelimumab

“…The protein product of TXNRD1 gene protects cells from oxidative stress, replenishes the deoxynucleotide triphosphate pool allowing for DNA synthesis and replication, and modulates the expression on macrophages of VSIG4, a B7 protein family protein member that regulates T-cell activation (43)(44)(45). The protein product of PLA2G7 regulates the ability of tumor cells to undergo apoptosis and alters inflammatory responses through the metabolism of platelet-activating factor (46,47).…”