ArticleGut2016
HNF4α is a therapeutic target that links AMPK to WNT signalling in early-stage gastric cancer.
Article in Gut, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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Who cites it
79 citing papers in PubMed, 116 citations in OpenAlex.
- Therapeutic effect of metformin on reversing gastric intestinal metaplasia.Chinese medical journal · 2026Trial
- Stomach at the crossroads: nuclear receptor signaling at the interface between what we are and what we eat.Physiological reviews · 2026Review
- The role of HNF4α in adenocarcinoma.Biochemical Society transactions · 2026Review
- Constitutive AMPK activation prevents hepatocellular carcinoma development through inhibition of HNF4α activity.Science advances · 2026Article
- HNF4α-HKDC1 axis orchestrates a metabolic rewiring to promote migration and metastasis in advanced gastric cancer.Cell death & disease · 2026Article
- A Clinically Derived TCM Decoction (WD-3) Attenuates Malignant Phenotypes of Gastric Cancer through the PPARγ-AMPK Pathway.Biological procedures online · 2026Article
- Chidamide enhances the sensitivity of gastric cancer to 5-fluorouracil chemotherapy by suppressing the HDAC3/HNF4A/TYMS axis.Cell death & disease · 2025Article
- Concurrent hypermethylation of CpG islands and hypomethylation of CpG-poor regions are associated with gastric cancer risk after Helicobacter pylori eradication.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2025Article
- Hepatocyte nuclear factor 4-Alpha: a key regulator in liver carcinogenesis.Cellular oncology (Dordrecht, Netherlands) · 2025Review
- NLRP3 inflammasome expression affects immune cell infiltration and clinical prognosis inMolecular medicine reports · 2025Article
- HNF4A promotes tumor progression in gastric cancer by transcriptional activation of KIF2C.Clinical and experimental medicine · 2025Article
- Expression patterns of HNF4α, TTF-1, and SMARCA4 in lung adenocarcinomas: impacts on clinicopathological and genetic features.Virchows Archiv : an international journal of pathology · 2025Article
- Identification and validation of tumor microenvironment-related therapeutic targets in gastric cancer using integrated multi-omics and molecular docking approaches.Frontiers in bioinformatics · 2025Article
- Multiview representation learning for identification of novel cancer genes and their causative biological mechanisms.Briefings in bioinformatics · 2024Article
- Drug repurposing for cancer therapy.Signal transduction and targeted therapy · 2024Review
- Metformin: A Dual-Role Player in Cancer Treatment and Prevention.International journal of molecular sciences · 2024Review
- Gastric intestinal metaplasia: progress and remaining challenges.Journal of gastroenterology · 2024Review
- HNF4A-Bridging the Gap Between Intestinal Metaplasia and Gastric Cancer.Evolutionary bioinformatics online · 2024Article
- Article
- ASAP1 activates the IQGAP1/CDC42 pathway to promote tumor progression and chemotherapy resistance in gastric cancer.Cell death & disease · 2023Article
19 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
20 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundWorldwide, gastric cancer (GC) is the fourth most common malignancy and the most common cancer in East Asia. Development of targeted therapies for this disease has focused on a few known oncogenes but has had limited effects.
objectiveTo determine oncogenic mechanisms and novel therapeutic targets specific for GC by identifying commonly dysregulated genes from the tumours of both Asian-Pacific and Caucasian patients.
methodsWe generated transcriptomic profiles of 22 Caucasian GC tumours and their matched non-cancerous samples and performed an integrative analysis across different GC gene expression datasets. We examined the inhibition of commonly overexpressed oncogenes and their constituent signalling pathways by RNAi and/or pharmacological inhibition.
resultsHepatocyte nuclear factor-4α (HNF4α) upregulation was a key signalling event in gastric tumours from both Caucasian and Asian patients, and HNF4α antagonism was antineoplastic. Perturbation experiments in GC tumour cell lines and xenograft models further demonstrated that HNF4α is downregulated by AMPKα signalling and the AMPK agonist metformin; blockade of HNF4α activity resulted in cyclin downregulation, cell cycle arrest and tumour growth inhibition. HNF4α also regulated WNT signalling through its target gene WNT5A, a potential prognostic marker of diffuse type gastric tumours.
conclusionsOur results indicate that HNF4α is a targetable oncoprotein in GC, is regulated by AMPK signalling through AMPKα and resides upstream of WNT signalling. HNF4α may regulate 'metabolic switch' characteristic of a general malignant phenotype and its target WNT5A has potential prognostic values. The AMPKα-HNF4α-WNT5A signalling cascade represents a potentially targetable pathway for drug development.
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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.