EMBO Molecular Medicine (Jan 2018)
Dual IRE1 RNase functions dictate glioblastoma development
- Stéphanie Lhomond,
- Tony Avril,
- Nicolas Dejeans,
- Konstantinos Voutetakis,
- Dimitrios Doultsinos,
- Mari McMahon,
- Raphaël Pineau,
- Joanna Obacz,
- Olga Papadodima,
- Florence Jouan,
- Heloise Bourien,
- Marianthi Logotheti,
- Gwénaële Jégou,
- Néstor Pallares‐Lupon,
- Kathleen Schmit,
- Pierre‐Jean Le Reste,
- Amandine Etcheverry,
- Jean Mosser,
- Kim Barroso,
- Elodie Vauléon,
- Marion Maurel,
- Afshin Samali,
- John B Patterson,
- Olivier Pluquet,
- Claudio Hetz,
- Véronique Quillien,
- Aristotelis Chatziioannou,
- Eric Chevet
Affiliations
- Stéphanie Lhomond
- Université de Bordeaux
- Tony Avril
- INSERM U1242, “Chemistry, Oncogenesis, Stress, Signaling”, Université de Rennes 1
- Nicolas Dejeans
- Université de Bordeaux
- Konstantinos Voutetakis
- Institute of Biology, Medicinal Chemistry & Biotechnology, NHRF
- Dimitrios Doultsinos
- INSERM U1242, “Chemistry, Oncogenesis, Stress, Signaling”, Université de Rennes 1
- Mari McMahon
- INSERM U1242, “Chemistry, Oncogenesis, Stress, Signaling”, Université de Rennes 1
- Raphaël Pineau
- INSERM U1242, “Chemistry, Oncogenesis, Stress, Signaling”, Université de Rennes 1
- Joanna Obacz
- INSERM U1242, “Chemistry, Oncogenesis, Stress, Signaling”, Université de Rennes 1
- Olga Papadodima
- Institute of Biology, Medicinal Chemistry & Biotechnology, NHRF
- Florence Jouan
- INSERM U1242, “Chemistry, Oncogenesis, Stress, Signaling”, Université de Rennes 1
- Heloise Bourien
- INSERM U1242, “Chemistry, Oncogenesis, Stress, Signaling”, Université de Rennes 1
- Marianthi Logotheti
- Institute of Biology, Medicinal Chemistry & Biotechnology, NHRF
- Gwénaële Jégou
- INSERM U1242, “Chemistry, Oncogenesis, Stress, Signaling”, Université de Rennes 1
- Néstor Pallares‐Lupon
- Université de Bordeaux
- Kathleen Schmit
- Université de Bordeaux
- Pierre‐Jean Le Reste
- INSERM U1242, “Chemistry, Oncogenesis, Stress, Signaling”, Université de Rennes 1
- Amandine Etcheverry
- Integrated Functional Genomics and Biomarkers Team, UMR6290, CNRS, Université de Rennes 1
- Jean Mosser
- Integrated Functional Genomics and Biomarkers Team, UMR6290, CNRS, Université de Rennes 1
- Kim Barroso
- INSERM U1242, “Chemistry, Oncogenesis, Stress, Signaling”, Université de Rennes 1
- Elodie Vauléon
- INSERM U1242, “Chemistry, Oncogenesis, Stress, Signaling”, Université de Rennes 1
- Marion Maurel
- INSERM U1242, “Chemistry, Oncogenesis, Stress, Signaling”, Université de Rennes 1
- Afshin Samali
- Apoptosis Research Centre, School of Natural Sciences, NUI Galway
- John B Patterson
- Medinnovata Inc.
- Olivier Pluquet
- Institut Pasteur de Lille, CNRS UMR8161 “Mechanisms of Tumourigenesis and Targeted Therapies”, Université de Lille
- Claudio Hetz
- Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile
- Véronique Quillien
- INSERM U1242, “Chemistry, Oncogenesis, Stress, Signaling”, Université de Rennes 1
- Aristotelis Chatziioannou
- Institute of Biology, Medicinal Chemistry & Biotechnology, NHRF
- Eric Chevet
- INSERM U1242, “Chemistry, Oncogenesis, Stress, Signaling”, Université de Rennes 1
- DOI
- https://doi.org/10.15252/emmm.201707929
- Journal volume & issue
-
Vol. 10,
no. 3
pp. 1 – 20
Abstract
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 IRE1α (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.
Keywords
