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BBC and GBM have stem cell\u2010like gene expression signatures, which are in part driven by forkhead box O (FOXO) transcription factors. To gain further insight into the impact of FOXO1 in BBC, we treated BT549 cells with AS1842856 and performed RNA sequencing. AS1842856 binds to unphosphorylated FOXO1 and inhibits its ability to directly bind to DNA. Gene Set Enrichment Analysis indicated that a set of WNT pathway target genes, including lymphoid enhancer\u2010binding factor 1 (<jats:italic>LEF1<\/jats:italic>) and transcription factor 7 (<jats:italic>TCF7<\/jats:italic>), were robustly induced after AS1842856 treatment. These same genes were also induced in GBM cell lines U87MG, LN18, LN229, A172, and DBTRG upon AS1842856 treatment. By contrast, follow\u2010up RNA interference (RNAi) targeting of <jats:italic>FOXO1<\/jats:italic> led to reduced <jats:italic>LEF1<\/jats:italic> and <jats:italic>TCF7<\/jats:italic> gene expression in BT549 and U87MG cells. In agreement with RNAi experiments, CRISPR Cas9\u2010mediated <jats:italic>FOXO1<\/jats:italic> disruption reduced the expression of canonical WNT genes <jats:italic>LEF1<\/jats:italic> and <jats:italic>TCF7<\/jats:italic> in U87MG cells. The loss of <jats:italic>TCF7<\/jats:italic> gene expression in <jats:italic>FOXO1<\/jats:italic> disruption mutants was restored by exogenous expression of the DNA\u2010binding\u2010deficient <jats:italic>FOXO1\u2010H215R<\/jats:italic>. Therefore, FOXO1 induces <jats:italic>TCF7<\/jats:italic> in a DNA\u2010binding\u2010independent manner, similar to other published FOXO1\u2010activated genes such as <jats:italic>TCF4<\/jats:italic> and hes family bHLH transcription factor 1. Our work demonstrates that <jats:italic>FOXO1<\/jats:italic> promotes canonical WNT gene expression in examined BBC and GBM cells, similar to results found in <jats:italic>Drosophila melanogaster<\/jats:italic>, T\u2010cell development, and murine acute myeloid leukemia models.<\/jats:p>","DOI":"10.1002\/2211-5463.13696","type":"journal-article","created":{"date-parts":[[2023,8,16]],"date-time":"2023-08-16T16:15:32Z","timestamp":1692202532000},"page":"2108-2123","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["FOXO1 promotes the expression of canonical WNT target genes in examined basal\u2010like breast and glioblastoma multiforme cancer cells"],"prefix":"10.1002","volume":"13","author":[{"given":"Shania","family":"Pintor","sequence":"first","affiliation":[{"name":"Department of Biology The University of Texas Rio Grande Valley  Edinburg TX 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