Dual IRE 1 RN ase functions dictate glioblastoma development
Authors: Tony Avril
Kim Barroso
Marianthi Logotheti
Aristotelis Chatziioannou
Gw√©na√´le J√©gou
Elodie Vaul√©on
Eric Chevet
Olivier Pluquet
Heloise Bourien
Olga Papadodima
Kathleen Schmit
Pierre-Jean Le Reste
Joanna Obacz
Marion Maurel
Nicolas Dejeans
Florence Jouan
V√©ronique Quillien
Amandine Etcheverry
N√©stor Pallares-Lupon
Rapha√´l Pineau
Afshin Samali
Mari McMahon
Konstantinos Voutetakis
John B Patterson
St√©phanie Lhomond
Dimitrios Doultsinos
Claudio Hetz
Jean Mosser
Journal: EMBO Molecular Medicine (2018)
Discipline: CLINICAL MEDICINE
Keywords: IRE1; XBP1; cancer; endoplasmic reticulum; regulated IRE1‚Äêdependent decay.
Affiliations: Universit√© de Bordeaux, Bordeaux, France., INSERM U1242, "Chemistry, Oncogenesis, Stress, Signaling", Universit√© de Rennes 1, Rennes, France., Centre de Lutte Contre le Cancer Eug√®ne Marquis, Rennes, France., Institute of Biology, Medicinal Chemistry & Biotechnology, NHRF, Athens, Greece., Department of Biochemistry & Biotechnology, University of Thessaly, Larissa, Greece., Apoptosis Research Centre, School of Natural Sciences, NUI Galway, Galway, Ireland., e-NIOS PC, Kallithea-Athens, Greece., Universit√© de Bordeaux Bordeaux France, Department of Neurosurgery, University Hospital Pontchaillou, Rennes, France., Integrated Functional Genomics and Biomarkers Team, UMR6290, CNRS, Universit√© de Rennes 1, Rennes, France., Medinnovata Inc., Ventura, CA, USA., Institut Pasteur de Lille, CNRS UMR8161 "Mechanisms of Tumourigenesis and Targeted Therapies", Universit√© de Lille, Lille, France., Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago, Chile., Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, University of Chile, Santiago, Chile., Center for Geroscience, Brain Health and Metabolism, Santiago, Chile., Buck Institute for Research on Aging, Novato, CA, USA., Department of Immunology and Infectious diseases, Harvard School of Public Health, Boston, MA, USA., INSERM U1242, "Chemistry, Oncogenesis, Stress, Signaling", Universit√© de Rennes 1, Rennes, France .

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 IRE1Œ± (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. 

Retracted: No

PubPeer comments:
 Figure 8A u2013 more similar than expected. Could authors check please?  , 
 Please ignore all red boxes. This is a comparison with the raw data provide by the authors. It seems that the original blot provided doesn t match the final figure for some conditions... https: www.hetzlab.cl wp-content uploads 2017 06 Data-backup-and-LAB-actions-from-comments-Pubpeer-2_compressed.pdf (Page 12)  , 
 I agree with Ripartites Tricholoma. The original Actin blots provided do NOT match the published blots. These original blots did not take away our concerns, but actually made them stronger, since they do not correspond to the blots in the paper. , 
 The questions are why the cleaved fragments observed IRE1 western blot for RNS96.1 are not shown and discussed in this paper, while those from RNS87.1 and RNS85.1 are highlighted (not the same MW so does not fit to the conclusion)? Also, Why the only line in the RNS130 Western blot matching to the original blots corresponds to the Q780* mutant ? The original blot shown by the authors definitively do not match and suggest that not only actin blots have been copy Invert paste but also that IRE1 data have been modified. Could the authors or EMBO Mol med clarify these points? ,