ArticleThe Journal of experimental medicine2011
A GATA4-regulated tumor suppressor network represses formation of malignant human astrocytomas.
Article in The Journal of experimental medicine, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 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
50 citing papers in PubMed, 2 syntheses or guidelines pooled it, 93 citations in OpenAlex.
- Pooled it
- Identification of 19 new risk loci and potential regulatory mechanisms influencing susceptibility to testicular germ cell tumor.Nature genetics · 2017Pooled it
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- Rootstock of distant hybrid activates transcription factors of scion cultivar to promote growth and yield in walnut.Plant biotechnology journal · 2025Article
- GATA Transcription Factors: A Cross-Road for Erythropoiesis, Neurodevelopment, and Synucleinopathies.Developmental neurobiology · 2025Review
- Brain-Specific Gata4 Downregulation in Greywick Female Mice Models the Metabolic Subtype of Polycystic Ovary Syndrome.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Nanoparticle encapsulation enables systemic IGF-Trap delivery to inhibit intracerebral glioma growth.Neuro-oncology · 2025Article
- Potential Prognostic Value of GATA4 Depends on the p53 Expression in Primary Glioblastoma Patients.Genes · 2023Article
- Progress on siRNA-based gene therapy targeting secondary injury after intracerebral hemorrhage.Gene therapy · 2023Review
- TP53-PTEN-NF1 depletion in human brain organoids produces a glioma phenotypeFrontiers in oncology · 2023Article
- Ubiquitin Proteasome Gene Signatures in Ependymoma Molecular Subtypes.International journal of molecular sciences · 2022Review
- A circular RNA derived from GLIS3 accelerates the proliferation of glioblastoma cells through competitively binding with miR-449c-5p to upregulate CAPG and GLIS3.BMC neuroscience · 2022Article
- SOX9 Protein in Pancreatic Cancer Regulates Multiple Cellular Networks in a Cell-Specific Manner.Biomedicines · 2022Article
- Review
- Comparative whole transcriptome analysis of gene expression in three canine soft tissue sarcoma types.PloS one · 2022Article
- Integrative analysis identifies an immune-relevant epigenetic signature for prognostication of non-G-CIMP glioblastomas.Oncoimmunology · 2021Article
- Transcriptomic and Proteomic Study on the High-Fat Diet Combined With AOM/DSS-Induced Adenomatous Polyps in Mice.Frontiers in oncology · 2021Article
- GATA-4, a potential novel therapeutic target for high-grade meningioma, regulates miR-497, a potential novel circulating biomarker for high-grade meningioma.EBioMedicine · 2020Article
- Prediction of cancer driver genes through network-based moment propagation of mutation scores.Bioinformatics (Oxford, England) · 2020Article
Corrections and comments
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Authors and funding
16 authors at 7 institutions in 3 countries.
Funding
Abstract
Glioblastoma Multiforme (GBM), the most common and lethal primary human brain tumor, exhibits multiple molecular aberrations. We report that loss of the transcription factor GATA4, a negative regulator of normal astrocyte proliferation, is a driver in glioma formation and fulfills the hallmarks of a tumor suppressor gene (TSG). Although GATA4 was expressed in normal brain, loss of GATA4 was observed in 94/163 GBM operative samples and was a negative survival prognostic marker. GATA4 loss occurred through promoter hypermethylation or novel somatic mutations. Loss of GATA4 in normal human astrocytes promoted high-grade astrocytoma formation, in cooperation with other relevant genetic alterations such as activated Ras or loss of TP53. Loss of GATA4 with activated Ras in normal astrocytes promoted a progenitor-like phenotype, formation of neurospheres, and the ability to differentiate into astrocytes, neurons, and oligodendrocytes. Re-expression of GATA4 in human GBM cell lines, primary cultures, and brain tumor-initiating cells suppressed tumor growth in vitro and in vivo through direct activation of the cell cycle inhibitor P21(CIP1), independent of TP53. Re-expression of GATA4 also conferred sensitivity of GBM cells to temozolomide, a DNA alkylating agent currently used in GBM therapy. This sensitivity was independent of MGMT (O-6-methylguanine-DNA-methyltransferase), the DNA repair enzyme which is often implicated in temozolomide resistance. Instead, GATA4 reduced expression of APNG (alkylpurine-DNA-N-glycosylase), a DNA repair enzyme which is poorly characterized in GBM-mediated temozolomide resistance. Identification and validation of GATA4 as a TSG and its downstream targets in GBM may yield promising novel therapeutic strategies.
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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.