ArticleThe Journal of clinical investigation2017
GATA4 loss of function in liver cancer impedes precursor to hepatocyte transition.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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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
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- Differentiation therapy and the mechanisms that terminate cancer cell proliferation without harming normal cells.Cell death & disease · 2018Pooled it
- FLT3-ITD signals for CEBPA and p53 proteolysis by the ubiquitin-proteosome pathway.Research square · 2026Article
- FLT3-ITD signals for CEBPA and p53 proteolysis by the ubiquitin-proteosome pathway.bioRxiv : the preprint server for biology · 2026Article
- Liquid biopsy-based multi-omics approach for early detection of hepatocellular carcinoma (ASCEND-Hep): a multiphase prospective development and validation study.BMC medicine · 2026Article
- GATA binding protein 4: Emerging role in liver development and diseases.Molecular biology reports · 2026Review
- LncRNA regulation of pyroptosis determines prognostic outcomes and functional characteristics in liver cancer.Discover oncology · 2026Article
- Targeting senescence and GATA4 in age-related cardiovascular disease: a comprehensive approach.Biogerontology · 2025Review
- GATA4 downregulation enhances CCL20-mediated immunosuppression in hepatocellular carcinoma.Hepatology communications · 2024Article
- CCDC25 suppresses clear cell renal cell carcinoma progression by LATS1/YAP-mediated regulation of the hippo pathway.Cancer cell international · 2024Article
- Atypical inflammatory kinase IKBKE phosphorylates and inactivates FoxA1 to promote liver tumorigenesis.Science advances · 2024Article
- Nuclear to cytoplasmic transport is a druggable dependency in MYC-driven hepatocellular carcinoma.Nature communications · 2024Article
- Neuroendocrine lineage commitment of small cell lung cancers can be leveraged into p53-independent non-cytotoxic therapy.Cell reports · 2023Article
- Changing paradigms in oncology: Toward noncytotoxic treatments for advanced gliomas.International journal of cancer · 2022Review
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- Article
- HNF1A POU Domain Mutations Found in Japanese Liver Cancer Patients Cause Downregulation ofGenes · 2022Article
- A GATA4-regulated secretory program suppresses tumors through recruitment of cytotoxic CD8 T cells.Nature communications · 2022Article
- SimultaneousAnnals of translational medicine · 2021Article
- GATA binding protein 4 promotes the expression and transcription of hepatitis B virus by facilitating hepatocyte nuclear factor 4 alpha in vitro.Virology journal · 2021Article
- PBRM1 loss in kidney cancer unbalances the proximal tubule master transcription factor hub to repress proximal tubule differentiation.Cell reports · 2021Article
Corrections and comments
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Authors and funding
29 authors at 3 institutions in 2 countries.
Funding
Abstract
The most frequent chromosomal structural loss in hepatocellular carcinoma (HCC) is of the short arm of chromosome 8 (8p). Genes on the remaining homologous chromosome, however, are not recurrently mutated, and the identity of key 8p tumor-suppressor genes (TSG) is unknown. In this work, analysis of minimal commonly deleted 8p segments to identify candidate TSG implicated GATA4, a master transcription factor driver of hepatocyte epithelial lineage fate. In a murine model, liver-conditional deletion of 1 Gata4 allele to model the haploinsufficiency seen in HCC produced enlarged livers with a gene expression profile of persistent precursor proliferation and failed hepatocyte epithelial differentiation. HCC mimicked this gene expression profile, even in cases that were morphologically classified as well differentiated. HCC with intact chromosome 8p also featured GATA4 loss of function via GATA4 germline mutations that abrogated GATA4 interactions with a coactivator, MED12, or by inactivating mutations directly in GATA4 coactivators, including ARID1A. GATA4 reintroduction into GATA4-haploinsufficient HCC cells or ARID1A reintroduction into ARID1A-mutant/GATA4-intact HCC cells activated hundreds of hepatocyte genes and quenched the proliferative precursor program. Thus, disruption of GATA4-mediated transactivation in HCC suppresses hepatocyte epithelial differentiation to sustain replicative precursor phenotype.
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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.