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 mul...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Springer Nature
2018-03-01
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| Series: | EMBO Molecular Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.15252/emmm.201707929 |
| _version_ | 1797283274218799104 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Stéphanie Lhomond |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-07T17:29:40Z |
| format | Article |
| id | doaj.art-fc9d46f9f6e245f98478a5229ed883cb |
| institution | Directory Open Access Journal |
| issn | 1757-4676 1757-4684 |
| language | English |
| last_indexed | 2024-03-07T17:29:40Z |
| publishDate | 2018-03-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj.art-fc9d46f9f6e245f98478a5229ed883cb2024-03-02T18:30:50ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842018-03-01103n/an/a10.15252/emmm.201707929Dual IRE1 RNase functions dictate glioblastoma developmentStéphanie Lhomond0Tony Avril1Nicolas Dejeans2Konstantinos Voutetakis3Dimitrios Doultsinos4Mari McMahon5Raphaël Pineau6Joanna Obacz7Olga Papadodima8Florence Jouan9Heloise Bourien10Marianthi Logotheti11Gwénaële Jégou12Néstor Pallares‐Lupon13Kathleen Schmit14Pierre‐Jean Le Reste15Amandine Etcheverry16Jean Mosser17Kim Barroso18Elodie Vauléon19Marion Maurel20Afshin Samali21John B Patterson22Olivier Pluquet23Claudio Hetz24Véronique Quillien25Aristotelis Chatziioannou26Eric Chevet27Université de Bordeaux Bordeaux FranceINSERM U1242, “Chemistry, Oncogenesis, Stress, Signaling” Université de Rennes 1 Rennes FranceUniversité de Bordeaux Bordeaux FranceInstitute of Biology, Medicinal Chemistry & Biotechnology NHRF Athens GreeceINSERM U1242, “Chemistry, Oncogenesis, Stress, Signaling” Université de Rennes 1 Rennes FranceINSERM U1242, “Chemistry, Oncogenesis, Stress, Signaling” Université de Rennes 1 Rennes FranceINSERM U1242, “Chemistry, Oncogenesis, Stress, Signaling” Université de Rennes 1 Rennes FranceINSERM U1242, “Chemistry, Oncogenesis, Stress, Signaling” Université de Rennes 1 Rennes FranceInstitute of Biology, Medicinal Chemistry & Biotechnology NHRF Athens GreeceINSERM U1242, “Chemistry, Oncogenesis, Stress, Signaling” Université de Rennes 1 Rennes FranceINSERM U1242, “Chemistry, Oncogenesis, Stress, Signaling” Université de Rennes 1 Rennes FranceInstitute of Biology, Medicinal Chemistry & Biotechnology NHRF Athens GreeceINSERM U1242, “Chemistry, Oncogenesis, Stress, Signaling” Université de Rennes 1 Rennes FranceUniversité de Bordeaux Bordeaux FranceUniversité de Bordeaux Bordeaux FranceINSERM U1242, “Chemistry, Oncogenesis, Stress, Signaling” Université de Rennes 1 Rennes FranceIntegrated Functional Genomics and Biomarkers Team UMR6290, CNRS Université de Rennes 1 Rennes FranceIntegrated Functional Genomics and Biomarkers Team UMR6290, CNRS Université de Rennes 1 Rennes FranceINSERM U1242, “Chemistry, Oncogenesis, Stress, Signaling” Université de Rennes 1 Rennes FranceINSERM U1242, “Chemistry, Oncogenesis, Stress, Signaling” Université de Rennes 1 Rennes FranceINSERM U1242, “Chemistry, Oncogenesis, Stress, Signaling” Université de Rennes 1 Rennes FranceApoptosis Research Centre School of Natural Sciences NUI Galway Galway IrelandMedinnovata Inc. Ventura CA USAInstitut Pasteur de Lille CNRS UMR8161 “Mechanisms of Tumourigenesis and Targeted Therapies” Université de Lille Lille FranceBiomedical Neuroscience Institute Faculty of Medicine University of Chile Santiago ChileINSERM U1242, “Chemistry, Oncogenesis, Stress, Signaling” Université de Rennes 1 Rennes FranceInstitute of Biology, Medicinal Chemistry & Biotechnology NHRF Athens GreeceINSERM U1242, “Chemistry, Oncogenesis, Stress, Signaling” Université de Rennes 1 Rennes FranceAbstract 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.https://doi.org/10.15252/emmm.201707929cancerendoplasmic reticulumIRE1regulated IRE1‐dependent decayXBP1 |
| spellingShingle | 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 Dual IRE1 RNase functions dictate glioblastoma development EMBO Molecular Medicine cancer endoplasmic reticulum IRE1 regulated IRE1‐dependent decay XBP1 |
| title | Dual IRE1 RNase functions dictate glioblastoma development |
| title_full | Dual IRE1 RNase functions dictate glioblastoma development |
| title_fullStr | Dual IRE1 RNase functions dictate glioblastoma development |
| title_full_unstemmed | Dual IRE1 RNase functions dictate glioblastoma development |
| title_short | Dual IRE1 RNase functions dictate glioblastoma development |
| title_sort | dual ire1 rnase functions dictate glioblastoma development |
| topic | cancer endoplasmic reticulum IRE1 regulated IRE1‐dependent decay XBP1 |
| url | https://doi.org/10.15252/emmm.201707929 |
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