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.

It was previously demonstrated that the ER stress sensor IRE1α (referred to as IRE1) contributes to GBM progression. The new study entitled “Dual IRE1 RNase functions dictate glioblastoma development” published in EMBO Molecular Medicine provides the first demonstration of a dual role of IRE1 downstream signaling in cancer and opens a new therapeutic window to abrogate tumor progression.

BioInfoMiner analysis was employed in order to define specific IRE1‐dependent gene expression signatures that were confronted to human GBM transcriptomes and shed light to the antagonistic roles of XBP1 mRNA splicing and RIDD on tumor outcomes, mainly through selective remodeling of the tumor stroma.

The research was carried out by an international consortium with the participation of e-NIOS, including among others Université de Bordeaux, Université de Rennes 1, University of Ireland Galway, University of Chile, INSERM, CNRS, National Hellenic Research Foundation and Harvard School of Public Health.