title: The M-type receptor PLA2R regulates senescence through the p53 pathway.
abstract: Senescence is a stable proliferative arrest induced by various stresses such as telomere erosion, oncogenic or oxidative stress. Compelling evidence suggests that it acts as a barrier against tumour development. Describing new mechanisms that favour an escape from senescence can thus reveal new insights into tumorigenesis. To identify new genes controlling the senescence programme, we performed a loss-of-function genetic screen in primary human fibroblasts. We report that knockdown of the M-type receptor PLA2R (phospholipase A2 receptor) prevents the onset of replicative senescence and diminishes stress-induced senescence. Interestingly, expression of PLA2R increases during replicative senescence, and its ectopic expression results in premature senescence. We show that PLA2R regulates senescence in a reactive oxygen species-DNA damage-p53-dependent manner. Taken together, our study identifies PLA2R as a potential new tumour suppressor gene crucial in the induction of cellular senescence through the activation of the p53 pathway.
authors.affiliation: UMR 8161, Institut de Biologie de Lille, CNRS/Universités de Lille 1 et 2/Institut Pasteur de Lille, IFR 142, 59021 Lille, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Augert
authors.forename: Christine
authors.initials: C
authors.lastname: Payré
authors.forename: Yvan
authors.initials: Y
authors.lastname: de Launoit
authors.forename: Jesus
authors.initials: J
authors.lastname: Gil
authors.forename: Gérard
authors.initials: G
authors.lastname: Lambeau
authors.forename: David
authors.initials: D
authors.lastname: Bernard
mesh_terms: D000818:Animals; D002460:Cell Line; D016922:Cellular Senescence / Q000502:physiology*; D015536:Down-Regulation; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D055785:Gene Knockdown Techniques; D006801:Humans; D017382:Reactive Oxygen Species / Q000378:metabolism; D054507:Receptors, Phospholipase A2 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D054507:Receptors, Phospholipase A2; D016159:Tumor Suppressor Protein p53