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024 7 _ |a 10.1093/neuonc/noad256
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024 7 _ |a 1523-5866
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037 _ _ |a DKFZ-2024-00944
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Obacz, Joanna
|b 0
245 _ _ |a IRE1 endoribonuclease signaling promotes myeloid cell infiltration in glioblastoma.
260 _ _ |a Oxford
|c 2024
|b Oxford Univ. Press
336 7 _ |a article
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336 7 _ |a Journal Article
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520 _ _ |a Intrinsic or environmental stresses trigger the accumulation of improperly folded proteins in the endoplasmic reticulum (ER), leading to ER stress. To cope with this, cells have evolved an adaptive mechanism named the unfolded protein response (UPR) which is hijacked by tumor cells to develop malignant features. Glioblastoma (GB), the most aggressive and lethal primary brain tumor, relies on UPR to sustain growth. We recently showed that IRE1 alpha (referred to IRE1 hereafter), 1 of the UPR transducers, promotes GB invasion, angiogenesis, and infiltration by macrophage. Hence, high tumor IRE1 activity in tumor cells predicts a worse outcome. Herein, we characterized the IRE1-dependent signaling that shapes the immune microenvironment toward monocytes/macrophages and neutrophils.We used human and mouse cellular models in which IRE1 was genetically or pharmacologically invalidated and which were tested in vivo. Publicly available datasets from GB patients were also analyzed to confirm our findings.We showed that IRE1 signaling, through both the transcription factor XBP1s and the regulated IRE1-dependent decay controls the expression of the ubiquitin-conjugating E2 enzyme UBE2D3. In turn, UBE2D3 activates the NFκB pathway, resulting in chemokine production and myeloid infiltration in tumors.Our work identifies a novel IRE1/UBE2D3 proinflammatory axis that plays an instrumental role in GB immune regulation.
536 _ _ |a 312 - Funktionelle und strukturelle Genomforschung (POF4-312)
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650 _ 7 |a ER stress
|2 Other
650 _ 7 |a IRE1
|2 Other
650 _ 7 |a chemokines
|2 Other
650 _ 7 |a glioblastoma
|2 Other
650 _ 7 |a inflammation
|2 Other
650 _ 7 |a Endoribonucleases
|0 EC 3.1.-
|2 NLM Chemicals
650 _ 7 |a Protein Serine-Threonine Kinases
|0 EC 2.7.11.1
|2 NLM Chemicals
650 _ 7 |a ERN1 protein, human
|0 EC 2.7.11.1
|2 NLM Chemicals
650 _ 2 |a Glioblastoma: pathology
|2 MeSH
650 _ 2 |a Glioblastoma: metabolism
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Endoribonucleases: metabolism
|2 MeSH
650 _ 2 |a Endoribonucleases: genetics
|2 MeSH
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Protein Serine-Threonine Kinases: metabolism
|2 MeSH
650 _ 2 |a Protein Serine-Threonine Kinases: genetics
|2 MeSH
650 _ 2 |a Signal Transduction
|2 MeSH
650 _ 2 |a Brain Neoplasms: pathology
|2 MeSH
650 _ 2 |a Brain Neoplasms: metabolism
|2 MeSH
650 _ 2 |a Myeloid Cells: metabolism
|2 MeSH
650 _ 2 |a Myeloid Cells: pathology
|2 MeSH
650 _ 2 |a Unfolded Protein Response
|2 MeSH
650 _ 2 |a Tumor Microenvironment
|2 MeSH
650 _ 2 |a Tumor Cells, Cultured
|2 MeSH
650 _ 2 |a Endoplasmic Reticulum Stress
|2 MeSH
700 1 _ |a Archambeau, Jérôme
|b 1
700 1 _ |a Lafont, Elodie
|b 2
700 1 _ |a Nivet, Manon
|b 3
700 1 _ |a Martin, Sophie
|b 4
700 1 _ |a Aubry, Marc
|b 5
700 1 _ |a Voutetakis, Konstantinos
|b 6
700 1 _ |a Pineau, Raphael
|b 7
700 1 _ |a Boniface, Rachel
|b 8
700 1 _ |a Sicari, Daria
|b 9
700 1 _ |a Pelizzari-Raymundo, Diana
|b 10
700 1 _ |a Ghukasyan, Gevorg
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700 1 _ |a McGrath, Eoghan
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700 1 _ |a Vlachavas, Efstathios-Iason
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700 1 _ |a Le Gallo, Matthieu
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700 1 _ |a Le Reste, Pierre Jean
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700 1 _ |a Barroso, Kim
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700 1 _ |a Fainsod-Levi, Tanya
|b 17
700 1 _ |a Obiedat, Akram
|b 18
700 1 _ |a Granot, Zvi
|b 19
700 1 _ |a Tirosh, Boaz
|b 20
700 1 _ |a Samal, Juhi
|b 21
700 1 _ |a Pandit, Abhay
|0 0000-0002-6292-4933
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700 1 _ |a Négroni, Luc
|b 23
700 1 _ |a Soriano, Nicolas
|b 24
700 1 _ |a Monnier, Annabelle
|b 25
700 1 _ |a Mosser, Jean
|b 26
700 1 _ |a Chatziioannou, Aristotelis
|0 P:(DE-HGF)0
|b 27
700 1 _ |a Quillien, Véronique
|b 28
700 1 _ |a Chevet, Eric
|b 29
700 1 _ |a Avril, Tony
|0 0000-0002-1129-8514
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773 _ _ |a 10.1093/neuonc/noad256
|g Vol. 26, no. 5, p. 858 - 871
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|p 858 - 871
|t Neuro-Oncology
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