IRE1 RNase controls CD95-mediated cell death.
CD95
Cell Death
ER Stress
IRE1
Unfolded Protein Response
Journal
EMBO reports
ISSN: 1469-3178
Titre abrégé: EMBO Rep
Pays: England
ID NLM: 100963049
Informations de publication
Date de publication:
21 Feb 2024
21 Feb 2024
Historique:
received:
31
03
2023
accepted:
03
02
2024
revised:
18
01
2024
medline:
22
2
2024
pubmed:
22
2
2024
entrez:
22
2
2024
Statut:
aheadofprint
Résumé
Signalling by the Unfolded Protein Response (UPR) or by the Death Receptors (DR) are frequently activated towards pro-tumoral outputs in cancer. Herein, we demonstrate that the UPR sensor IRE1 controls the expression of the DR CD95/Fas, and its cell death-inducing ability. Both genetic and pharmacologic blunting of IRE1 activity increased CD95 expression and exacerbated CD95L-induced cell death in glioblastoma (GB) and Triple-Negative Breast Cancer (TNBC) cell lines. In accordance, CD95 mRNA was identified as a target of Regulated IRE1-Dependent Decay of RNA (RIDD). Whilst CD95 expression is elevated in TNBC and GB human tumours exhibiting low RIDD activity, it is surprisingly lower in XBP1s-low human tumour samples. We show that IRE1 RNase inhibition limited CD95 expression and reduced CD95-mediated hepatic toxicity in mice. In addition, overexpression of XBP1s increased CD95 expression and sensitized GB and TNBC cells to CD95L-induced cell death. Overall, these results demonstrate the tight IRE1-mediated control of CD95-dependent cell death in a dual manner through both RIDD and XBP1s, and they identify a novel link between IRE1 and CD95 signalling.
Identifiants
pubmed: 38383861
doi: 10.1038/s44319-024-00095-9
pii: 10.1038/s44319-024-00095-9
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Fondation ARC pour la Recherche sur le Cancer (ARC)
ID : PDF20171206671
Organisme : Fondation ARC pour la Recherche sur le Cancer (ARC)
ID : PJA20181207700
Organisme : Fondation de France (Foundation of France)
ID : N/A
Organisme : EC | H2020 | PRIORITY 'Excellent science' | H2020 Marie Skłodowska-Curie Actions (MSCA)
ID : ITN-675448
Organisme : Institut National Du Cancer (INCa)
ID : PLBIO 2018,2019
Organisme : Ligue Contre le Cancer (French League Against Cancer)
ID : N/A
Organisme : Association La Vannetaise
ID : N/A
Organisme : Association La Josselinaise des femmes
ID : N/A
Organisme : Centre Eugène Marquis
ID : N/A
Organisme : Université de Rennes 1 (University of Rennes 1)
ID : Défis Scientifiques
Informations de copyright
© 2024. The Author(s).
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