ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2012
Hypoxia induces IGFBP3 in esophageal squamous cancer cells through HIF-1α-mediated mRNA transcription and continuous protein synthesis.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- A meta-analysis of HIF-1α and esophageal squamous cell carcinoma (ESCC) risk.Pathology oncology research : POR · 2013Pooled it
- BCAT1-dependent HIF-1α stabilization is a targetable metabolic vulnerability in hepatocellular carcinoma.Cell reports. Medicine · 2026Article
- Insulin-like growth factor binding protein-3 serves as a biomarker for resistance to enzalutamide in prostate cancer.Apoptosis : an international journal on programmed cell death · 2026Article
- Maternal high-fat, high-sucrose diet-induced excess adiposity is linked to placental hypoxia and disruption of fetoplacental immune homeostasis in late gestation†.Biology of reproduction · 2025Article
- Paracrine IGFBP3 spatially coordinates IGF signaling to induce myocardial regeneration in mice.Journal of molecular and cellular cardiology · 2025Article
- Hypoxia and loss of GCM1 expression prevent differentiation and contact inhibition in human trophoblast stem cells.Stem cell reports · 2025Article
- Linking hypoxia-inducible factor (HIF)-1α and HIF-2α expression in head and neck cancer.Bioinformation · 2025Article
- Single cell atlas of kidney cancer endothelial cells reveals distinct expression profiles and phenotypes.BJC reports · 2024Article
- Molecular subtyping and characterization of clear cell renal cell carcinoma by tumor differentiation trajectories.iScience · 2023Article
- Single cell atlas of kidney cancer endothelial cells reveals distinct expression profiles and phenotypes.Research square · 2023Article
- Secretome analysis reveals reduced expression of COL4A2 in hypoxic cancer-associated fibroblasts with a tumor-promoting function in gastric cancer.Journal of cancer research and clinical oncology · 2023Article
- Roles of IGFBP-3 in cell migration and growth in an endophytic tongue squamous cell carcinoma cell line.Scientific reports · 2022Article
- SOX17-mediated MALAT1-miR-199a-HIF1α axis confers sensitivity in esophageal squamous cell carcinoma cells to radiotherapy.Cell death discovery · 2022Article
- Response to Different Oxygen Partial Pressures and Evolution Analysis of Apoptosis-Related Genes in Plateau Zokor (Frontiers in genetics · 2022Article
- Differential expression of hypoxia-inducible factors related to the invasiveness of epithelial ovarian cancer.Scientific reports · 2021Article
- Alcohol Metabolism Enriches Squamous Cell Carcinoma Cancer Stem Cells That Survive Oxidative Stress via Autophagy.Biomolecules · 2021Article
- Cancer Plasticity: The Role of mRNA Translation.Trends in cancer · 2021Review
- Cyclovirobuxine inhibits the progression of clear cell renal cell carcinoma by suppressing the IGFBP3-AKT/STAT3/MAPK-Snail signalling pathway.International journal of biological sciences · 2021Article
- The Choice of Candidates in Survival Markers Based on Coordinated Gene Expression in Renal Cancer.Frontiers in oncology · 2021Article
- Hsa_circ_0046263 functions as a ceRNA to promote nasopharyngeal carcinoma progression by upregulating IGFBP3.Cell death & disease · 2020Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
Insulin-like growth factor binding protein (IGFBP)-3 regulates cell proliferation and apoptosis in esophageal squamous cell carcinoma (ESCC) cells. We have investigated how the hypoxic tumor microenvironment in ESCC fosters the induction of IGFBP3. RNA interference experiments revealed that hypoxia-inducible factor (HIF)-1α, but not HIF-2α, regulates IGFBP3 mRNA induction. By chromatin immunoprecipitation and transfection assays, HIF-1α was found to transactivate IGFBP3 through a novel hypoxia responsive element (HRE) located at 57 kb upstream from the transcription start site. Metabolic labeling experiments demonstrated hypoxia-mediated inhibition of global protein synthesis. 7-Methyl GTP-cap binding assays suggested that hypoxia suppresses cap-dependent translation. Experiments using pharmacological inhibitors for mammalian target of rapamycin (mTOR) suggested that a relatively weak mTOR activity may be sufficient for cap-dependent translation of IGFBP3 under hypoxic conditions. Bicistronic RNA reporter transfection assays did not validate the possibility of an internal ribosome entry site as a potential mechanism for cap-independent translation for IGFBP3 mRNA. Finally, IGFBP3 mRNA was found enriched to the polysomes. In aggregate, our study establishes IGFBP3 as a direct HIF-1α target gene and that polysome enrichment of IGFBP3 mRNA may permit continuous translation under hypoxic conditions.
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