ArticleThe Journal of biological chemistry2011
WT1 protein directly regulates expression of vascular endothelial growth factor and is a mediator of tumor response to hypoxia.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 2 of them syntheses that pooled it.
What it found
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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
35 citing papers in PubMed, 2 syntheses or guidelines pooled it, 63 citations in OpenAlex.
- Wilms' tumor 1 (WT1) as a prognosis factor in gynecological cancers: A meta-analysis.Medicine · 2018Pooled it
- Wilms' tumor 1 (WT1) expression and prognosis in solid cancer patients: a systematic review and meta-analysis.Scientific reports · 2015Pooled it
- Review
- Spiny Mice Show a Profibrotic Epicardial Mesothelial Response to Hypoxic Injury Comparable to C57BL/6 Mice.Biomolecules · 2026Article
- SGK1 repression by WT1 may confer a survival advantage to leukemic cells under stress conditions.Annals of hematology · 2025Article
- Enhanced neoangiogenesis and balance of the immune response mediated by the Wilms' tumor suppressor WT1 favor repair after myocardial infarction.Theranostics · 2025Article
- Wilms' tumor 1 (WT1) antigen is overexpressed in Kaposi Sarcoma and is regulated by KSHV vFLIP.PLoS pathogens · 2024Article
- A Nucleus-Targeting WT1 Antagonistic Peptide Encapsulated in Polymeric Nanomicelles Combats Refractory Chronic Myeloid Leukemia.Pharmaceutics · 2023Article
- Microenvironmental control of hematopoietic stem cell fate via CXCL8 and protein kinase C.Cell reports · 2023Article
- Hypoxia and HIFs in Ewing sarcoma: new perspectives on a multi-facetted relationship.Molecular cancer · 2023Review
- Regulation of Mesothelial Cell Fate during Development and Human Diseases.International journal of molecular sciences · 2022Review
- Every Beat You Take-The Wilms' Tumor Suppressor WT1 and the Heart.International journal of molecular sciences · 2021Review
- Determinants of resistance to VEGF-TKI and immune checkpoint inhibitors in metastatic renal cell carcinoma.Journal of experimental & clinical cancer research : CR · 2021Review
- Implications of the Wilms' Tumor Suppressor Wt1 in Cardiomyocyte Differentiation.International journal of molecular sciences · 2021Article
- Truncated WT1 Protein Isoform Expression Is Increased in MCF-7 Cells with Long-Term Estrogen Depletion.International journal of breast cancer · 2021Article
- Role of immunotherapy in Ewing sarcoma.Journal for immunotherapy of cancer · 2020Review
- Molecular Characteristics and Treatment of Endothelial Dysfunction in Patients with COPD: A Review Article.International journal of molecular sciences · 2019Review
- Article
- Limitations to the Therapeutic Potential of Tyrosine Kinase Inhibitors and Alternative Therapies for Kidney Cancer.Ochsner journal · 2019Review
- WT1 expression in vessels varies with histopathological grade in tumour-bearing and control tissue from patients with breast cancer.British journal of cancer · 2018Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
WT1 is a zinc finger transcription factor expressed at high levels in many types of solid tumors, and high WT1 expression is an adverse prognostic factor. How WT1 contributes to tumor growth and influences prognosis remains unclear. We investigated the hypothesis that WT1 up-regulates VEGF in solid tumors, augmenting the response to hypoxia. We found a correlation between levels of WT1 expression and VEGF expression in Ewing sarcoma cell lines. Transfecting WT1-null SK-ES-1 cells with WT1 up-regulated VEGF mRNA expression and resulted in increased angiogenic activity in vitro. Conversely, diminishing WT1 expression in WT1-positive cell lines using WT1-specific shRNA down-regulated VEGF mRNA expression and decreased angiogenic activity in vitro. Transient transfection assays demonstrated that WT1 can regulate the activity of the VEGF promoter, and chromatin immunoprecipitation assays showed that WT1 can bind directly to the VEGF promoter in intact cells. WT1 expression in Ewing sarcoma cells is up-regulated by hypoxia. Importantly, using shRNA to inhibit this up-regulation blunted the hypoxia-mediated increase in VEGF expression. Taken together, these data demonstrate that VEGF is a direct, bona fide WT1 target gene in sarcoma and that WT1 plays a key role in optimizing the response of tumor cells to hypoxia.
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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.