ArticleOncogene2021
FOXO3 is a latent tumor suppressor for FOXO3-positive and cytoplasmic-type gastric cancer cells.
Article in Oncogene, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- Multi-omic network analysis identified betacellulin as a novel target of omega-3 fatty acid attenuation of western diet-induced nonalcoholic steatohepatitis.EMBO molecular medicine · 2023Pooled it
- Adaptive Evolution of FOXO Family Regulating Lifespan Extension and Cancer Resistance in Long-Lived Species.Integrative zoology · 2026Article
- miR-1307-3p promotes the progression of cervical cancer by targeting FOXO3.Irish journal of medical science · 2026Article
- Longevity-associatedTranslational lung cancer research · 2026Article
- LINC00222 regulates FOXO3 to interfere with β-catenin signaling pathway and suppresses prostate cancer progression.Scientific reports · 2026Article
- A powerful representation learning method for enhanced analysis of incomplete multi-omics data.NPJ systems biology and applications · 2026Article
- Dual inhibition of glycolysis and glutaminolysis by targeting FOXO3 for hepatocellular carcinoma treatment.Oncogene · 2026Article
- Chronic psychological stress disrupts liver homeostasis by dysregulating oxidative phosphorylation via the PI3K/AKT/FoxO3a axis.iScience · 2026Article
- CircFoxo3 knockdown inhibit gastric cancer progression by regulating Foxo3.In vitro cellular & developmental biology. Animal · 2026Article
- Genetic drivers of Chinese hamster ovary cell proliferation revealed by functional genomics.iScience · 2025Article
- Gastric Cancer Treatment New Chapter: Organoid Models Leading Personalized Medicine.Molecular diagnosis & therapy · 2025Review
- DAF-16/FOXO maintains genome integrity following genotoxic stress.bioRxiv : the preprint server for biology · 2025Article
- Ginsenosides Enhanced Apoptosis of Serum-Free Starved A549 Lung Cancer Cells.Molecules (Basel, Switzerland) · 2025Article
- L2S2: chemical perturbation and CRISPR KO LINCS L1000 signature search engine.Nucleic acids research · 2025Article
- DNA methylation patterns in breast cancer, paired benign tissue from ipsilateral and contralateral breast, and healthy controls.Breast cancer research : BCR · 2025Article
- circRNA_0005927 inhibits gastric cancer metastasis by downregulating the miR-570-3p/FOXO3 axis.American journal of translational research · 2025Article
- Transcriptome analysis reveals a role of FOXO3 in antileukemia/lymphoma properties of panduratin A.Scientific reports · 2024Article
- Nuclear MAST4 Suppresses FOXO3 through Interaction with AKT3 and Induces Chemoresistance in Pancreatic Ductal Carcinoma.International journal of molecular sciences · 2024Article
- Genome-wide DNA methylation analysis of Astragalus and Danshen on the intervention of myofibroblast activation in idiopathic pulmonary fibrosis.BMC pulmonary medicine · 2023Article
- The APC/C E3 ligase subunit ANAPC11 mediates FOXO3 protein degradation to promote cell proliferation and lymph node metastasis in urothelial bladder cancer.Cell death & disease · 2023Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
FOXO3 is a member of the FOXO transcription factors thought to play a tumor-suppressor role in gastrointestinal cancer, while tumor-promoting function of FOXO3 has also been reported. These results suggest a context-dependent function of FOXO3 in tumor development. However, the relationship between the FOXO3 expression pattern and its role in tumorigenesis has not been elucidated. We examined the FOXO3 expression in 65 human primary gastric cancer and patient-derived xenograft tissues by immunohistochemistry and identified three subtypes according to subcellular localization: FOXO3-nuclear accumulated (FOXO3-Nuc), FOXO3-nuclear/cytoplasmic or cytoplasmic distributed (FOXO3-Cyt), and FOXO3-negative. In the FOXO3-Cyt gastric cancer cells, the expression of the constitutive active mutant FOXO3 (Act-ER FOXO3) induced the nuclear accumulation of FOXO3 and significantly suppressed colony formation and proliferation. The inhibition of the PI3K-AKT pathway by inhibitor treatment also suppressed the proliferation of FOXO3-Cyt gastric cancer cells, which was associated with the nuclear accumulation of endogenous FOXO3. Furthermore, the expression of Act-ER FOXO3 by an endogenous promoter significantly suppressed gastric tumorigenesis in Gan mice, a model of gastric cancer. Finally, treatment of FOXO3-Cyt human gastric cancer-derived organoids with an AKT inhibitor significantly suppressed the survival and proliferation. These results indicate that FOXO3 is a latent tumor suppressor for FOXO3-Cyt-type gastric cancer cells and that activation of the PI3K-AKT pathway protects this type of gastric cancer cell from FOXO3-mediated growth suppression via constitutive nuclear export. Thus, the inhibition of the PI3K-AKT pathway and nuclear translocation of endogenous FOXO3 may have therapeutic applications in the treatment of FOXO3-positive and cytoplasmic-type gastric cancer.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.