ArticleJournal of cancer research and clinical oncology2020
The PI3K pathway impacts stem gene expression in a set of glioblastoma cell lines.
Article in Journal of cancer research and clinical oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 20 citations in OpenAlex.
- Single-cell multi-omics reveals DUSP9 as a key regulator of cancer stemness and a potential therapeutic target in hepatocellular carcinoma.Journal of translational medicine · 2026Article
- Pathophysiological and Etiological Corroborations for the Mechanistic Design of Intranasal Therapies in Glioblastoma Multiforme.Current pharmaceutical design · 2026Review
- FoxO1 signaling in B cell malignancies and its therapeutic targeting.FEBS letters · 2025Review
- Unlocking Cellular Memory and Gene Regulatory Networks: Pioneering the Future of Therapeutic Innovations.Cells · 2025Article
- Emerging Therapies for Glioblastoma.Cancers · 2024Review
- Proteomic Assessment of SKBR3/HER2+ Breast Cancer Cellular Response to Lapatinib and Investigational Ipatasertib Kinase Inhibitors.bioRxiv : the preprint server for biology · 2024Article
- Article
- Proteomic assessment of SKBR3/HER2+ breast cancer cellular response to Lapatinib and investigational Ipatasertib kinase inhibitors.Frontiers in pharmacology · 2024Article
- FOXO1 promotes the expression of canonical WNT target genes in examined basal-like breast and glioblastoma multiforme cancer cells.FEBS open bio · 2023Article
- Forkhead box transcription factors (FOXOs and FOXM1) in glioma: from molecular mechanisms to therapeutics.Cancer cell international · 2023Review
- The FOXO1 inhibitor AS1842856 triggers apoptosis in glioblastoma multiforme and basal-like breast cancer cells.FEBS open bio · 2023Article
- TMEM60 Promotes the Proliferation and Migration and Inhibits the Apoptosis of Glioma through Modulating AKT Signaling.Journal of oncology · 2022Article
- PI3K Pathway Inhibition with NVP-BEZ235 Hinders Glycolytic Metabolism in Glioblastoma Multiforme Cells.Cells · 2021Article
- Review
- NVP-BEZ235 or JAKi Treatment leads to decreased survival of examined GBM and BBC cells.Cancer treatment and research communications · 2021Article
- The Role and Specific Mechanism of OCT4 in Cancer Stem Cells: A Review.International journal of stem cells · 2020Review
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24 authors at 1 institution in 1 country.
Funding
Abstract
backgroundThe PI3K pathway controls diverse cellular processes including growth, survival, metabolism, and apoptosis. Nuclear FOXO factors were observed in cancers that harbor constitutively active PI3K pathway output and stem signatures. FOXO1 and FOXO3 were previously published to induce stem genes such as OCT4 in embryonic stem cells. Here, we investigated FOXO-driven stem gene expression in U87MG glioblastoma cells.
methodsPI3K-activated cancer cell lines were investigated for changes in gene expression, signal transduction, and clonogenicity under conditions with FOXO3 disruption or exogenous expression. The impact of PI3K pathway inhibition on stem gene expression was examined in a set of glioblastoma cell lines.
resultsWe found that CRISPR-Cas9-mediated FOXO3 disruption in U87MG cells caused decreased OCT4 and SOX2 gene expression, STAT3 phosphorylation on tyrosine 705 and clonogenicity. FOXO3 over expression led to increased OCT4 in numerous glioblastoma cancer cell lines. Strikingly, treatment of glioblastoma cells with NVP-BEZ235 (a dual inhibitor of PI3K and mTOR), which activates FOXO factors, led to robust increases OCT4 gene expression. Direct FOXO factor recruitment to the OCT4 promoter was detected by chromatin immunoprecipitation analyses using U87MG extracts. DISCUSSION: We show for the first time that FOXO transcription factors promote stem gene expression glioblastoma cells. Treatment with PI3K inhibitor NVP-BEZ235 led to dramatic increases in stem genes in a set of glioblastoma cell lines.
conclusionGiven that, PI3K inhibitors are actively investigated as targeted cancer therapies, the FOXO-mediated induction of stem genes observed in this study highlights a potential hazard to PI3K inhibition. Understanding the molecular underpinnings of stem signatures in cancer will allow refinements to therapeutic strategies. Targeting FOXO factors to reduce stem cell characteristics in concert with PI3K inhibition may prove therapeutically efficacious.
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