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PLA2R1: expression and function in Cancer

Authors
  • Bernard, David
  • Vindrieux, David1, 2, 3, 4
  • 1 INSERM U1052, Centre de Recherche en Cancérologie de Lyon, Lyon, F-69373
  • 2 CNRS UMR5286, Lyon, F-69373
  • 3 Centre Léon Bérard, Lyon, F-69373
  • 4 Université de Lyon, Lyon, F-69373
Type
Published Article
Journal
Biochimica et Biophysica Acta (BBA) - Reviews on Cancer
Publisher
Elsevier
Publication Date
Jan 01, 2014
Accepted Date
Mar 19, 2014
Identifiers
DOI: 10.1016/j.bbcan.2014.03.003
Source
Elsevier
Keywords
License
Unknown

Abstract

The phospholipase A2 receptor 1 (PLA2R1 or PLA2R) was isolated twenty years ago for its ability to bind several secretory phospholipase A2 proteins (sPLA2). Since its identification, it has attracted only a limited interest, mainly in the sPLA2 biology field, as it is viewed uniquely as a regulator of sPLA2 activities. Recent discoveries outline novel important functions of this gene in cancer biology. Indeed, PLA2R1 gain or loss of function experiments in vitro and in vivo show that this receptor promotes several tumor suppressive responses including senescence, apoptosis and inhibition of transformation. Supporting a tumor suppressive role of PLA2R1, its expression decreases in numerous cancers, and known oncogenes such as HIF2α and c-MYC repress its expression. PLA2R1 promoter methylation, a classical way to repress tumor suppressive gene expression in cancer cells, is observed in leukemia, in kidney and in breast cancer cells. Mechanistically, PLA2R1 activates the kinase JAK2 and orients its activity towards a tumor suppressive one. PLA2R1 also promotes accumulation of reactive oxygen species which induce cell death and senescence. This review compiles recent data demonstrating an unexpected tumor suppressive role of PLA2R1 and outlines the future work needed to improve our knowledge of the functions of this gene in cancer.

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