ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2011
Tumor suppressor FOXO3 mediates signals from the EGF receptor to regulate proliferation of colonic cells.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
23 citing papers in PubMed, 31 citations in OpenAlex.
- Changes in EGFR activity following CRISPR/Cas9-editing of the EGF binding domain.Scientific reports · 2026Article
- Lung adenocarcinoma surfaceome remodeling with EGFR inhibitors uncovers placental alkaline phosphatase as a target for combination therapy.Cell reports. Medicine · 2025Article
- FOXO3: at the crossroads of metabolic, inflammatory, and tumorigenic remodeling in the colon.American journal of physiology. Gastrointestinal and liver physiology · 2024Review
- The Janus-Faced Role of Lipid Droplets in Aging: Insights from the Cellular Perspective.Biomolecules · 2023Review
- FOXO3 Expression in Macrophages Is Lowered by a High-Fat Diet and Regulates Colonic Inflammation and Tumorigenesis.Metabolites · 2022Article
- Transcription factors in colorectal cancer: molecular mechanism and therapeutic implications.Oncogene · 2021Review
- Esomeprazole affects the proliferation, metastasis, apoptosis and chemosensitivity of gastric cancer cells by regulating lncRNA/circRNA-miRNA-mRNA ceRNA networks.Oncology letters · 2020Article
- Lipid droplets: platforms with multiple functions in cancer hallmarks.Cell death & disease · 2020Review
- EGFR/FOXO3A/LXR-α Axis Promotes Prostate Cancer Proliferation and Metastasis and Dual-Targeting LXR-α/EGFR Shows Synthetic Lethality.Frontiers in oncology · 2020Article
- The forkhead-box family of transcription factors: key molecular players in colorectal cancer pathogenesis.Molecular cancer · 2019Review
- Loss of Forkhead Box O3 Facilitates Inflammatory Colon Cancer: Transcriptome Profiling of the Immune Landscape and Novel Targets.Cellular and molecular gastroenterology and hepatology · 2019Article
- NEDD4-induced degradative ubiquitination of phosphatidylinositol 4-phosphate 5-kinase α and its implication in breast cancer cell proliferation.Journal of cellular and molecular medicine · 2018Article
- Effect of Genistein on Apoptosis and Proliferation of Hepatocellular Carcinoma Hepa1-6 Cell Line.International journal of preventive medicine · 2018Article
- Epidermal growth factor receptor mediated proliferation depends on increased lipid droplet density regulated via a negative regulatory loop with FOXO3/Sirtuin6.Biochemical and biophysical research communications · 2016Article
- Type 3 Muscarinic Receptors Contribute to Clearance of Citrobacter rodentium.Inflammatory bowel diseases · 2015Article
- Threonine 32 (Thr32) of FoxO3 is critical for TGF-β-induced apoptosis via Bim in hepatocarcinoma cells.Protein & cell · 2015Article
- MicroRNA expressions associated with progression of prostate cancer cells to antiandrogen therapy resistance.Molecular cancer · 2014Article
- Decreased FOXO3 within advanced human colon cancer: implications of tumour suppressor function.British journal of cancer · 2013Article
- FOXO3 expression during colorectal cancer progression: biomarker potential reflects a tumour suppressor role.British journal of cancer · 2013Article
- FOXO3 growth inhibition of colonic cells is dependent on intraepithelial lipid droplet density.The Journal of biological chemistry · 2013Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Epithelial proliferation, critical for homeostasis, healing, and colon cancer progression, is in part controlled by epidermal growth factor receptor (EGFR). Proliferation of colonic epithelia can be induced by Citrobacter rodentium infection, and we have demonstrated that activity of tumor suppressor FOXO3 was attenuated after this infection. Thus the aim of this study was to determine the contribution of FOXO3 in EGFR-dependent proliferation of intestinal epithelia and colon cancer cell lines. In this study we show that, during infection with C. rodentium, EGFR was significantly phosphorylated in colonic mucosa and Foxo3 deficiency in this model lead to an increased number of bromodeoxyuridine-positive cells. In vitro, in human colon cancer cells, increased expression and activation of EGFR was associated with proliferation that leads to FOXO3 phosphorylation (inactivation). Following EGFR activation, FOXO3 was phosphorylated (via phosphatidylinositol 3-kinase/Akt) and translocated to the cytosol where it was degraded. Moreover, inhibition of proliferation by overexpressing FOXO3 was not reversed by the EGFR signaling, implicating FOXO3 as one of the regulators downstream of EGFR. FOXO3 binding to the promoter of the cell cycle inhibitor p27kip1 was decreased by EGFR signaling, suggesting its role in EGFR-dependent proliferation. In conclusion, we show that proliferation in colonic epithelia and colon cancer cells, stimulated by EGFR, is mediated via loss of FOXO3 activity and speculate that FOXO3 may serve as a target in the development of new pharmacological treatments of proliferative diseases.
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Registered trials
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.