Abstract 1475: FOXO transcription factors regulate WNT pathway gene expression in GBM

Abstract

Basal-like breast cancer (BBC) and Glioblastoma Multiforme (GBM) are aggressive cancers associated with poor prognosis. BBC and GBM express stem gene expression signatures which are in part driven by FOXO transcription factors. To gain further insight into the impact of FOXO1 in BBC, we treated BT549 cells with the FOXO1 inhibitor AS1842856 and performed RNA Seq. Gene Set Enrichment Analysis (GSEA) with RNA Seq. data indicated that a set of WNT target genes including LEF1 and AXIN2 were robustly induced after 48-hours of AS1842856 treatment. These same genes were also induced in GBM cell lines U87MG, LN18, LN229, A172, and DBTRG upon AS1842856 treatment. RNAi targeting of FOXO1 led to reduced LEF1 gene expression in BT549 and U87MG cells at 18-hour and 24-hour timepoints respectively. CRISPR Cas9-mediated FOXO1 disruption led to reduced expression of canonical WNT target gene LEF1 in U87MG cells. Citation Format: Megan Keniry, Shania Pintor, Alma Lopez, David Flores. FOXO transcription factors regulate WNT pathway gene expression in GBM [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1475.