Open AccessDual IRE 1 RN ase functions dictate glioblastoma development
Author(s) -
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,
PallaresLupon Néstor,
Schmit Kathleen,
Le Reste PierreJean,
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
Publication year - 2018
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.201707929
Subject(s) - glioblastoma , dual (grammatical number) , chemistry , microbiology and biotechnology , biology , computational biology , cancer research , literature , art
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 IRE 1α (referred to as IRE 1) contributes to GBM progression, through XBP 1 mRNA splicing and regulated IRE 1‐dependent decay ( RIDD ) of RNA . Here, we first demonstrated IRE 1 signaling significance to human GBM and defined specific IRE 1‐dependent gene expression signatures that were confronted to human GBM transcriptomes. This approach allowed us to demonstrate the antagonistic roles of XBP 1 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 IRE 1 downstream signaling in cancer and opens a new therapeutic window to abrogate tumor progression.