PLA2R1 kills cancer cells by inducing mitochondrial stress

Arnaud Augert, David Vindrieux, Christophe A Girard, Benjamin Le Calvé, Baptiste Gras, Mylène Ferrand, Benjamin P Bouchet, Alain Puisieux, Yvan de Launoit, Hélène Simonnet, Gérard Lambeau, David Bernard

Résultats de recherche: Contribution à un journal/une revueArticle

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.

langue originaleAnglais
Pages (de - à)969-77
Nombre de pages9
journalFree Radicals in Biology and Medicine
Volume65
Les DOIs
étatPublié - 2013
Modification externeOui

Empreinte digitale

Secretory Phospholipase A2
Cell death
Cells
Reactive Oxygen Species
Cell Death
Phospholipase A2 Receptors
Neoplasms
Breast Neoplasms
Cell Line
Cell growth
Electron Transport
Screening
Breast
Epithelial Cells
Apoptosis
Growth
Experiments

Citer ceci

Augert, Arnaud ; Vindrieux, David ; Girard, Christophe A ; Le Calvé, Benjamin ; Gras, Baptiste ; Ferrand, Mylène ; Bouchet, Benjamin P ; Puisieux, Alain ; de Launoit, Yvan ; Simonnet, Hélène ; Lambeau, Gérard ; Bernard, David. / PLA2R1 kills cancer cells by inducing mitochondrial stress. Dans: Free Radicals in Biology and Medicine. 2013 ; Vol 65. p. 969-77.
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title = "PLA2R1 kills cancer cells by inducing mitochondrial stress",
abstract = "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.",
keywords = "Apoptosis, Cell Line, Tumor, Cell Proliferation, DNA Fragmentation, Electron Transport Chain Complex Proteins, Gene Expression, Humans, Mitochondria, Oxidative Stress, Reactive Oxygen Species, Receptors, Phospholipase A2, Journal Article, Research Support, Non-U.S. Gov't",
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year = "2013",
doi = "10.1016/j.freeradbiomed.2013.08.177",
language = "English",
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pages = "969--77",
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Augert, A, Vindrieux, D, Girard, CA, Le Calvé, B, Gras, B, Ferrand, M, Bouchet, BP, Puisieux, A, de Launoit, Y, Simonnet, H, Lambeau, G & Bernard, D 2013, 'PLA2R1 kills cancer cells by inducing mitochondrial stress', Free Radicals in Biology and Medicine, VOL. 65, p. 969-77. https://doi.org/10.1016/j.freeradbiomed.2013.08.177

PLA2R1 kills cancer cells by inducing mitochondrial stress. / Augert, Arnaud; Vindrieux, David; Girard, Christophe A; Le Calvé, Benjamin; Gras, Baptiste; Ferrand, Mylène; Bouchet, Benjamin P; Puisieux, Alain; de Launoit, Yvan; Simonnet, Hélène; Lambeau, Gérard; Bernard, David.

Dans: Free Radicals in Biology and Medicine, Vol 65, 2013, p. 969-77.

Résultats de recherche: Contribution à un journal/une revueArticle

TY - JOUR

T1 - PLA2R1 kills cancer cells by inducing mitochondrial stress

AU - Augert, Arnaud

AU - Vindrieux, David

AU - Girard, Christophe A

AU - Le Calvé, Benjamin

AU - Gras, Baptiste

AU - Ferrand, Mylène

AU - Bouchet, Benjamin P

AU - Puisieux, Alain

AU - de Launoit, Yvan

AU - Simonnet, Hélène

AU - Lambeau, Gérard

AU - Bernard, David

N1 - © 2013 Elsevier Inc. All rights reserved.

PY - 2013

Y1 - 2013

N2 - 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.

AB - 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.

KW - Apoptosis

KW - Cell Line, Tumor

KW - Cell Proliferation

KW - DNA Fragmentation

KW - Electron Transport Chain Complex Proteins

KW - Gene Expression

KW - Humans

KW - Mitochondria

KW - Oxidative Stress

KW - Reactive Oxygen Species

KW - Receptors, Phospholipase A2

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.freeradbiomed.2013.08.177

DO - 10.1016/j.freeradbiomed.2013.08.177

M3 - Article

C2 - 23994771

VL - 65

SP - 969

EP - 977

JO - Free Radicals in Biology and Medicine

JF - Free Radicals in Biology and Medicine

SN - 0891-5849

ER -