Abstract 1453: Investigating the Role of FOXO4 in glioblastoma

Abstract Evolutionarily conserved partially redundant Forkhead box transcription factors FOXO -1, -3, and -4 drive stem cell maintenance in embryonic, cancer, mesenchymal, hematopoietic, and neural stem cells. Canonically, high PI3K output leads to cytoplasmic/inactive FOXO factors. Stem cells, however, are fundamentally rewired to have high PI3K Pathway activity and nuclear/active FOXO factors. Our previously published work and the work of others show that FOXO factors directly bind to and activate stem genes in both embryonic stem cells and the poor prognosis of cancer glioblastoma multiforme (GBM) to drive stem cell fate. However, the precise mechanisms utilized by FOXO transcription factors in driving stemness, hindering differentiation, and promoting cancer are incompletely understood. To gain insight into the role of nuclear FOXO4 in glioblastoma, we disrupted the gene encoding this factor using CRISPR Cas9 genome editing and performed RNA-seq in the U87MG background. We identified 2, 519 differentially expressed genes in FOXO4-deleted U87MG cells compared to unmodified controls, including those that drive invasion. Current work is examining whether FOXO4 promotes invasion of glioblastoma cells. Citation Format: Megan Keniry, David Uribe. Investigating the Role of FOXO4 in glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1453.