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Dual ire1 rnase functions dictate glioblastoma development

Lhomond, Stéphanie
; 
Avril, Tony
; 
Dejeans, Nicolas
; 
Voutetakis, Konstantinos
; 
Doultsinos, Dimitrios
; 
McMahon, Mari
; 
Pineau, Raphaël
; 
Obacz, Joanna
; 
Papadodima, Olga
; 
Jouan, Florence
... show 10 more
Identifiers
http://hdl.handle.net/10379/12439
https://doi.org/10.13025/25557
Repository DOI
10.15252/emmm.201707929
Publication Date
2018-01-08
Keywords
cancer, endoplasmic reticulum, ire1, regulated ire1-dependent decay, xbp1, unfolded protein response, requiring enzyme 1-alpha, xbp-1 messenger-rna, er stress, endoplasmic-reticulum, ire1-alpha, pathway, cancer, glioma, expression
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Article
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Citation
Lhomond, Stéphanie; Avril, Tony; Dejeans, Nicolas; Voutetakis, Konstantinos; Doultsinos, Dimitrios; McMahon, Mari; Pineau, Raphaël; Obacz, Joanna; Papadodima, Olga; Jouan, Florence; Bourien, Heloise; Logotheti, Marianthi; Jégou, Gwénaële; Pallares‐Lupon, Néstor; Schmit, Kathleen; Le Reste, Pierre‐Jean; Etcheverry, Amandine; Mosser, Jean; Barroso, Kim; Vauléon, Elodie; Maurel, Marion; Samali, Afshin; Patterson, John B; Pluquet, Olivier; Hetz, Claudio; Quillien, Véronique; Chatziioannou, Aristotelis; Chevet, Eric (2018). Dual ire1 rnase functions dictate glioblastoma development. EMBO Molecular Medicine 10 (3),
Abstract
Proteostasis imbalance is emerging as a major hallmark of cancer, driving tumor aggressiveness. Evidence suggests that the endoplasmic reticulum (ER), a major site for protein folding and quality control, plays a critical role in cancer development. This concept is valid in glioblastoma multiform (GBM), the most lethal primary brain cancer with no effective treatment. We previously demonstrated that the ER stress sensor IRE1 alpha (referred to as IRE1) contributes to GBM progression, through XBP1 mRNA splicing and regulated IRE1-dependent decay (RIDD) of RNA. Here, we first demonstrated IRE1 signaling significance to human GBM and defined specific IRE1-dependent gene expression signatures that were confronted to human GBM transcriptomes. This approach allowed us to demonstrate the antagonistic roles of XBP1 mRNA splicing and RIDD on tumor outcomes, mainly through selective remodeling of the tumor stroma. This study provides the first demonstration of a dual role of IRE1 downstream signaling in cancer and opens a new therapeutic window to abrogate tumor progression.
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Publisher
EMBO
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Attribution-NonCommercial-NoDerivs 3.0 Ireland
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Externally hosted open access publications with University of Galway authors (2)