Pulmonary Arterial Hypertension KnowledgeBase (bioinfom_tsdb)
bioinfom_tsdb
Pulmonary Arterial Hypertension KnowledgeBase
General information | Literature | Expression | Regulation | Mutation | Interaction

Basic Information

Gene ID

7941

Name

PLA2G7

Synonymous

LDL-PLA2|LP-PLA2|PAFAD|PAFAH;phospholipase A2, group VII (platelet-activating factor acetylhydrolase, plasma);PLA2G7;phospholipase A2, group VII (platelet-activating factor acetylhydrolase, plasma)

Definition

1-alkyl-2-acetylglycerophosphocholine esterase|2-acetyl-1-alkylglycerophosphocholine esterase|LDL-PLA(2)|LDL-associated phospholipase A2|PAF 2-acylhydrolase|PAF acetylhydrolase|gVIIA-PLA2|group-VIIA phospholipase A2|lipoprotein-associated phospholipase A2

Position

6p21.2-p12

Gene type

protein-coding

Title

Abstract

PLA2R1 mediates tumor suppression by activating JAK2.

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.

')