Year: 2026
Type: preprint
Abstract: Glioblastoma is a highly aggressive brain tumour driven by therapy-resistant glioblastoma stem cells (GSCs) that switch between dormant and proliferative states through poorly defined programs. In this study, we identify SAT1 , encoding the rate-limiting polyamine-catabolic enzyme SSAT1, as enriched in quiescent GSCs, linking metabolic rewiring to dormancy. Pharmacologic induction of SSAT1 with the polyamine analogue N 1 ,N 11 -Diethylnorspermine (DENSpm) triggers a chemoprotective, reversible growth arrest in patient-derived GSCs, independent of stemness, differentiation or senescence. SAT1- induced dormancy coincides with reduced eIF5A hypusination and global protein translation, and a marked rise in double-stranded RNA that activates type I interferon signalling. Knocking down the mitochondrial antiviral-signalling protein, essential for antiviral innate immunity, partially reverses this growth arrest, establishing viral mimicry as functionally required for dormancy. Single-cell and cohort analyses across GSCs and neural stem cells demonstrate that susceptibility to metabolically induced quiescence is set by an intrinsic inflammatory tone and lysosomal dependency, defining a context- dependent metabolic-immune axis which can be targeted to prevent GBM progression.
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7220462681