PLA2R1 kills cancer cells by inducing mitochondrial stress - Centre de recherche en cancérologie de Lyon (UMR INSERM 1052 ; CNRS 5286 ; Centre Léon Bérard) Accéder directement au contenu
Article Dans Une Revue Free Radical Biology and Medicine Année : 2013

PLA2R1 kills cancer cells by inducing mitochondrial stress

Résumé

Little is known about the biological functions of the phospholipase A2 receptor (PLA2R1) except that it has the ability to bind a few secreted phospholipases A2 (sPLA2's). We have previously shown that PLA2R1 regulates senescence in normal human cells. In this study, we investigated the ability of PLA2R1 to control cancer cell growth. Analysis of expression in cancer cells indicates a marked PLA2R1 decrease in breast cancer cell lines compared to normal or nontransformed human mammary epithelial cells. Accordingly, PLA2R1 ectopic expression in PLA2R1-negative breast cancer cell lines led to apoptosis, whereas a prosenescence response was predominantly triggered in normal cells. PLA2R1 structure-function studies and the use of chemical inhibitors of sPLA2-related signaling pathways suggest that the effect of PLA2R1 is sPLA2-independent. Functional experiments demonstrate that PLA2R1 regulation of cell death is driven by a reactive oxygen species (ROS)-dependent mechanism. While screening for ROS-producing complexes involved in PLA2R1 biological responses, we identified a critical role for the mitochondrial electron transport chain in PLA2R1-induced ROS production and cell death. Taken together, this set of data provides evidence for an important role of PLA2R1 in controlling cancer cell death by influencing mitochondrial biology.

Dates et versions

hal-02395811 , version 1 (05-12-2019)

Identifiants

Citer

Arnaud Augert, David Vindrieux, Christophe Girard, Benjamin Le Calvé, Baptiste Gras, et al.. PLA2R1 kills cancer cells by inducing mitochondrial stress. Free Radical Biology and Medicine, 2013, 65, pp.969-977. ⟨10.1016/j.freeradbiomed.2013.08.177⟩. ⟨hal-02395811⟩
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