Skip to Main content Skip to Navigation
Journal articles

Dual IRE1 RNase functions dictate glioblastoma development

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.
Document type :
Journal articles
Complete list of metadatas

Cited literature [38 references]  Display  Hide  Download

https://hal-univ-rennes1.archives-ouvertes.fr/hal-01777737
Contributor : Laurent Jonchère <>
Submitted on : Wednesday, April 25, 2018 - 9:42:32 AM
Last modification on : Friday, May 29, 2020 - 11:18:04 AM
Long-term archiving on: : Wednesday, September 19, 2018 - 8:18:16 PM

File

EMMM-10-e7929.pdf
Publisher files allowed on an open archive

Licence


Distributed under a Creative Commons Attribution 4.0 International License

Identifiers

Citation

Stéphanie Lhomond, Tony Avril, Nicolas Dejeans, Konstantinos Voutetakis, Dimitrios Doultsinos, et al.. Dual IRE1 RNase functions dictate glioblastoma development. EMBO Molecular Medicine, Wiley Open Access, 2018, 10 (3), pp.e7929. ⟨10.15252/emmm.201707929⟩. ⟨hal-01777737⟩

Share

Metrics

Record views

535

Files downloads

263