ArticleClinical and translational medicine2021
Hypoxia-induced FOXO4/LDHA axis modulates gastric cancer cell glycolysis and progression.
Article in Clinical and translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 76 citations in OpenAlex.
- The role of plasma exosomal lnc-SNAPC5-3:4 in monitoring the efficacy of anlotinib in the treatment of advanced non-small cell lung cancer.Journal of cancer research and clinical oncology · 2022Trial
- The evolving landscape of the Warburg effect in gastric cancer: From molecular mechanisms to targeted therapy.Clinical and translational medicine · 2026Review
- Hypoxia-inducible factors: Regulatory functions and status as a therapeutic target in gastric cancer (Review).Oncology letters · 2026Review
- Metabolic reprogramming networks in the gastric cancer tumor microenvironment: an integrated axis of nutrient competition, metabolic crosstalk, and immunosuppression.Frontiers in immunology · 2026Review
- Article
- Multi-omics analyses identify mannose phosphate isomerase-centered hypoxia-induced angiogenesis signature in colorectal cancer.Journal of translational medicine · 2025Article
- Identification and validation of RAS signaling-related genes for prognostic prediction and immunological characterization in gastric cancer.Translational cancer research · 2025Article
- Unveiling Metabolic Signatures as Potential Biomarkers in Common Cancers: Insights from Lung, Breast, Colorectal, Liver, and Gastric Tumours.Biomolecules · 2025Review
- STING contributes to the inflammation and proliferation ofInfection and immunity · 2025Article
- P4HA1 is highly expressed in gastric cancer and promotes proliferation and metastasis of gastric cancer cells.Discover oncology · 2025Article
- Fragile X messenger ribonucleoprotein 1 (FMRP) regulates glycolytic gene expression under chronic hypoxia in HCT116 cells.Scientific reports · 2025Article
- Comprehensive analysis of glycometabolism-related genes reveals PLOD2 as a prognostic biomarker and therapeutic target in gastric cancer.BMC gastroenterology · 2025Article
- Effects of hypoxia stress on the milk synthesis in bovine mammary epithelial cells.Journal of animal science and biotechnology · 2025Article
- ACAA2 Protects Against Cardiac Dysfunction and Lipid Peroxidation in Renal Insufficiency with the Treatment of S-Nitroso-L-Cysteine.Biomolecules · 2025Article
- "Friends or foes": a new perspective of tumour metabolic transcriptional modification.Cell death & disease · 2025Review
- To describe the subsets of malignant epithelial cells in gastric cancer, their developmental trajectories and drug resistance characteristics.Discover oncology · 2025Article
- Advances in glycolysis research in gastric cancer: molecular mechanisms, regulatory networks, and therapeutic potential.Frontiers in oncology · 2025Review
- Physiological and molecular mechanisms of tolerance to hypoxia and oxygen deficiency resistance markers.Frontiers in molecular biosciences · 2025Review
- FLLL31 Induces Apoptosis via the FOXO4/BCL6 Axis to Inhibit Bladder Cancer Progression.Human mutation · 2025Article
- Harnessing glycolysis in gastric cancer: molecular targets, therapeutic strategies, and clinical horizons.Frontiers in immunology · 2025Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
aimWe previously identified forkhead box (FOX) O4 mRNA as a predictor in gastric cancer (GC). However, the underlying mechanism has yet to be elucidated. We aimed to illustrate the mechanism by which FOXO4 regulated glycolysis under hypoxia in GC.
methodsFOXO4 protein expression was investigated by immunohistochemical staining of 252 GC and their normal adjacent tissues. We restored or silenced FOXO4 expression in GC cell lines to explore the underlying mechanisms.
resultsFOXO4 was downregulated in GC. Loss of FOXO4 expression was validated in univariate and multivariate survival analysis as an independent prognostic predictor for overall survival (P < 0.05) and disease-free survival (P<0.05). Restored FOXO4 expression significantly impaired the glycolysis rate in GC cells, while silencing FOXO4 expression enhanced glycolysis rate. FOXO4 expression was inversely associated with maximum standardized uptake value in mice models and patient samples. Mechanistically, FOXO4 bound to the glycolytic enzyme lactate dehydrogenase (LDH)A promoter and inactivated its activity in a dose-dependent manner (P < 0.05). Finally, we determined that FOXO4 was a transcriptional target of hypoxia-inducible factor (HIF) -1α, which is central in response to hypoxia.
conclusionsOur data suggested that FOXO4 plays a key role in the regulation of glycolysis in GC, and disrupting the HIF-1α-FOXO4-LDHA axis might be a promising therapeutic strategy for GC.
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