Peer-Reviewed Journal Details
Mandatory Fields
Lhomond, S,Avril, T,Dejeans, N,Voutetakis, K,Doultsinos, D,McMahon, M,Pineau, R,Obacz, J,Papadodima, O,Jouan, F,Bourien, H,Logotheti, M,Jegou, G,Pallares-Lupon, N,Schmit, K,Le Reste, PJ,Etcheverry, A,Mosser, J,Barroso, K,Vauleon, E,Maurel, M,Samali, A,Patterson, JB,Pluquet, O,Hetz, C,Quillien, V,Chatziioannou, A,Chevet, E
2018
March
Embo Molecular Medicine
Dual IRE1 RNase functions dictate glioblastoma development
Published
Optional Fields
cancer endoplasmic reticulum IRE1 regulated IRE1-dependent decay XBP1 UNFOLDED PROTEIN RESPONSE REQUIRING ENZYME 1-ALPHA XBP-1 MESSENGER-RNA ER STRESS ENDOPLASMIC-RETICULUM IRE1-ALPHA PATHWAY CANCER GLIOMA EXPRESSION
10
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 IRE1 alpha (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.
10.15252/emmm.201707929
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