Title |
Dual IRE1 RNase functions dictate glioblastoma development
|
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Published in |
EMBO Molecular Medicine, January 2018
|
DOI | 10.15252/emmm.201707929 |
Pubmed ID | |
Authors |
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 |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
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France | 4 | 11% |
United Kingdom | 3 | 8% |
Germany | 3 | 8% |
Austria | 2 | 6% |
Greece | 2 | 6% |
Ireland | 2 | 6% |
Canada | 2 | 6% |
Italy | 1 | 3% |
United States | 1 | 3% |
Other | 2 | 6% |
Unknown | 14 | 39% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 17 | 47% |
Scientists | 17 | 47% |
Science communicators (journalists, bloggers, editors) | 2 | 6% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 131 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 31 | 24% |
Researcher | 15 | 11% |
Student > Bachelor | 12 | 9% |
Student > Doctoral Student | 11 | 8% |
Student > Master | 11 | 8% |
Other | 15 | 11% |
Unknown | 36 | 27% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 42 | 32% |
Agricultural and Biological Sciences | 16 | 12% |
Medicine and Dentistry | 13 | 10% |
Neuroscience | 4 | 3% |
Immunology and Microbiology | 3 | 2% |
Other | 10 | 8% |
Unknown | 43 | 33% |