Necrotic Cells Alter IRE1α-XBP1 Signaling and Induce Transcriptional Changes in Glioblastoma.

ABSTRACT: Necrosis is a characteristic feature of glioblastoma multiforme (GBM) and is closely associated with tumor-associated inflammation and poor clinical outcomes. However, the molecular consequences of necrotic cell death on endoplasmic reticulum (ER) stress signaling in GBM cells remain unclear. In this study, we examined the effects of necrotic cells on the ER stress signaling and unfolded protein response (UPR) in human glioblastoma cell lines. Exposure to necrotic cells reduced IRE1α phosphorylation and increased unspliced XBP1 (XBP1u) accumulation, without affecting PERK or ATF6 pathways. These changes were accompanied by enhanced IκBα phosphorylation and impaired autophagic degradation. Treatment with ER stress inducers failed to reverse XBP1u accumulation, and reduced phosphorylation of

SUBMITTER: Lim J 

PROVIDER: S-EPMC12786997 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature