ODC-Driven Polyamines Synthesis Sustains the Self-Renewal of Glioblastoma Stem Cells and Drives Tumor Aggressiveness.

ABSTRACT: Glioblastoma stem cells (GSCs) are crucial drivers of tumor progression and therapeutic resistance in glioblastoma multiforme (GBM), yet the molecular mechanisms maintaining their self-renewal remain incompletely understood. Here, we identify a critical role for polyamine metabolism in GSCs maintenance. We show that GSCs exhibit elevated polyamine levels compared to non-stem tumor cells, attributed to enhanced ornithine decarboxylase (ODC) expression. High ODC expression correlates with poor patient prognosis in GBM. Genetic and pharmacologic targeting of ODC attenuated GSCs self-renewal and tumorigenicity. Our findings reveal a previously unrecognized metabolic dependency of GSCs on polyamine synthesis, and ODC may be a potential therapeutic target in GBM.

SUBMITTER: Wei XC 

PROVIDER: S-EPMC12580865 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature