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Article Dans Une Revue EMBO Reports Année : 2024

IRE1 RNase controls CD95-mediated cell death

Diana Pelizzari Raymundo
Manon Nivet
Raphaël Pineau
Alexandra Papaioannou
Xingchen Zhou
Sophie Martin
Matthieu Le Gallo
Tony Avril
Eric Chevet
Elodie Lafont

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.

Domaines

Cancer

Dates et versions

hal-04483618 , version 1 (29-02-2024)

Identifiants

Citer

Diana Pelizzari Raymundo, Victoria Maltret, Manon Nivet, Raphaël Pineau, Alexandra Papaioannou, et al.. IRE1 RNase controls CD95-mediated cell death. EMBO Reports, 2024, Embo Reports, 25 (4), pp.1792-1813. ⟨10.1038/s44319-024-00095-9⟩. ⟨hal-04483618⟩
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