Published October 14, 2013
| Version v1
Journal article
PLA2R1 Mediates Tumor Suppression by Activating JAK2
Creators
- Vindrieux, David
- Augert, Arnaud
- Girard, Christophe
- Gitenay, Delphine
- Lallet-Daher, Helene
- Wiel, Clotilde
- Le Calvé, Benjamin
- Gras, Baptiste
- Ferrand, Mylène
- Verbeke, Stéphanie
- de Launoit, Yvan
- Leroy, Xavier
- Puisieux, Alain
- Aubert, Sébastien
- Perrais, Michael
- Gelb, Michael
- Simonnet, Hélène
- Lambeau, Gérard
- Bernard, David
Contributors
Others:
- Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL) ; Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL) ; Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
- Institut de biologie de Lille - IBL (IBLI) ; Université de Lille, Sciences et Technologies-Institut Pasteur de Lille ; Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS)
- Institut de pharmacologie moléculaire et cellulaire (IPMC) ; Université Nice Sophia Antipolis (1965 - 2019) (UNS) ; COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)
- Validation et identification de nouvelles cibles en oncologie (VINCO) ; Institut Bergonié [Bordeaux] ; UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM)
- Institut de Pathologie [CHU Lille] ; Pôle de Biologie Pathologie Génétique [CHU Lille] ; Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)
- Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc) ; Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille
- University of Washington [Seattle]
- Institut de pharmacologie moléculaire et cellulaire (IPMC) ; Université Nice Sophia Antipolis (1965 - 2019) (UNS) ; COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)
- This work was carried out with the support of the Association pour la Recherche sur le Cancer, the Association for International Cancer Research for D. Bernard and G. Lambeau; the Institut National du Cancer, the "RTRS Fondation Synergie Lyon Cancer" for D. Bernard; and of the ANR (ANR-09-JCJC-0002) for M. Perrais.
- The authors thank the laboratory members for helpful discussions. The authors thank S. Courtois-Cox, H. Mertani, P. Mehlen, C. Abbadie, R. Iggo, S. Léon, I. Treilleux, I. Plo, and LMT facility for helpful discussions and reagents.
- ANR-09-JCJC-0002,MUC1kid,Rôle de MUC1 au cours de la carcinogenèse et de la régénération rénales(2009)
Description
Little is known about the physiological role of the phospholipase A2 receptor (PLA2R1). PLA2R1 has been described as regulating the replicative senescence, a telomerase-dependent proliferation arrest. The downstream PLA2R1 signaling and its role in cancer are currently unknown. Senescence induction in response to activated oncogenes is a failsafe program of tumor suppression that must be bypassed for tumorigenesis. We now present evidence that PLA2R1 functions in vitro as a tumor suppressor, the depletion of which is sufficient to escape oncogene-induced senescence (OIS), thereby facilitating oncogenic cell transformation. Furthermore, mice that are genetically deficient in PLA2R1 display increased sensitivity to RAS-induced tumorigenesis by facilitating OIS escape, highlighting its physiological role as a tumor suppressor. Unexpectedly, PLA2R1 activated JAK2 and its effector signaling, with PLA2R1-mediated inhibition of cell transformation largely reverted in JAK2-depleted cells. This finding was unexpected as the JAK2 pathway has been associated mainly with protumoral functions and several inhibitors are currently in clinical trials. Taken together, our findings uncover an unanticipated tumor suppressive role for PLA2R1 that is mediated by targeting downstream JAK2 effector signaling.
Abstract
International audienceAdditional details
Identifiers
- URL
- https://hal.archives-ouvertes.fr/hal-02395807
- URN
- urn:oai:HAL:hal-02395807v1
Origin repository
- Origin repository
- UNICA