ArticleProtein & cell2021
Metformin inhibits pancreatic cancer metastasis caused by SMAD4 deficiency and consequent HNF4G upregulation.
Article in Protein & cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 50 papers, 1 of them a synthesis that pooled it.
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Who cites it
50 citing papers in PubMed, 1 synthesis or guideline pooled it, 87 citations in OpenAlex.
- Association of Metformin with the Mortality and Incidence of Cardiovascular Events in Patients with Pre-existing Cardiovascular Diseases.Drugs · 2022 · on this mapPooled it
- Metabolites and cancer metastasis.Oncogene · 2026Review
- Comparison of Metformin Combinations with Other Repurposed Drugs in the Treatment of Hamster Fibrosarcoma: A Review.Pharmaceuticals (Basel, Switzerland) · 2026Review
- LLPS-based classification and a novel prognostic signature reveal NRF1 as a therapeutic target in pancreatic cancer.Cancer cell international · 2026Article
- Integrative Proteogenomic Characterization of Left-Sided and Right-Sided Colorectal Cancer.MedComm · 2026Article
- Senescence-driven molecular subtyping in pancreatic cancer: a multi-omics framework for precision medicine.BMC cancer · 2025Article
- Transcription factor switching drives subtype-specific pancreatic cancer.Nature genetics · 2025Article
- Review
- Tumor-associated macrophages (TAMs): Constructing an immunosuppressive microenvironment bridge for pancreatic ductal adenocarcinoma (PDAC).Cancer pathogenesis and therapy · 2025Review
- Pancreatic endocrine and exocrine signaling and crosstalk in physiological and pathological status.Signal transduction and targeted therapy · 2025Review
- The role of AMPK in pancreatic cancer: from carcinogenesis to treatment.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Review
- Repurposing of Metabolic Drugs Metformin and Simvastatin as an Emerging Class of Cancer Therapeutics.Pharmaceutical research · 2025Review
- EAP: A versatile cloud-based platform for efficient quantitative analysis of large-scale ChIP/ATAC-seq datasets.Computational and structural biotechnology journal · 2025Article
- Metformin and its Nanoformulations in Cancer Prevention and Therapy.Current pharmaceutical design · 2025Review
- Synergistic effects of calcium channel blockers and renin-angiotensin inhibitors with gemcitabine-based chemotherapy on the survival of patients with pancreatic cancer.Journal of cancer research and clinical oncology · 2024Article
- Targeted Therapies in Pancreatic Cancer: A New Era of Precision Medicine.Biomedicines · 2024Review
- Emerging mechanisms and promising approaches in pancreatic cancer metabolism.Cell death & disease · 2024Review
- Investigating the impact of SMAD2 and SMAD4 downregulation in colorectal cancer and their correlation with immune markers, prognosis, and drug resistance and sensitivity.Molecular biology reports · 2024Article
- Immune-related signature identifies IL1R2 as an immunological and prognostic biomarker in pancreatic cancer.Journal of pancreatology · 2024Article
- KDM5B promotes SMAD4 loss-driven drug resistance through activating DLG1/YAP to induce lipid accumulation in pancreatic ductal adenocarcinoma.Cell death discovery · 2024Article
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pancreatic ductal adenocarcinoma (PDAC) has poor prognosis due to limited therapeutic options. This study examines the roles of genome-wide association study identified PDAC-associated genes as therapeutic targets. We have identified HNF4G gene whose silencing most effectively repressed PDAC cell invasiveness. HNF4G overexpression is induced by the deficiency of transcriptional factor and tumor suppressor SMAD4. Increased HNF4G are correlated with SMAD4 deficiency in PDAC tumor samples and associated with metastasis and poor survival time in xenograft animal model and in patients with PDAC (log-rank P = 0.036; HR = 1.60, 95% CI = 1.03-2.47). We have found that Metformin suppresses HNF4G activity via AMPK-mediated phosphorylation-coupled ubiquitination degradation and inhibits in vitro invasion and in vivo metastasis of PDAC cells with SMAD4 deficiency. Furthermore, Metformin treatment significantly improve clinical outcomes and survival in patients with SMAD4-deficient PDAC (log-rank P = 0.022; HR = 0.31, 95% CI = 0.14-0.68) but not in patients with SMAD4-normal PDAC. Pathway analysis shows that HNF4G may act in PDAC through the cell-cell junction pathway. These results indicate that SMAD4 deficiency-induced overexpression of HNF4G plays a critical oncogenic role in PDAC progression and metastasis but may form a druggable target for Metformin treatment.
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