ArticleThe Journal of clinical investigation2017
Hepatocyte nuclear factor 1α suppresses steatosis-associated liver cancer by inhibiting PPARγ transcription.
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 54 papers.
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Who cites it
54 citing papers in PubMed, 71 citations in OpenAlex.
- Elucidating the beneficial effects of gut microbiota-derived metabolites in treating hepatocellular carcinoma: an integrated network pharmacology, molecular docking, and single-cell sequencing analysis.Bioresources and bioprocessing · 2026Article
- Network-based toxicological analysis of core targets and pathways of bisphenol A-driven hepatocellular carcinoma.Biochemistry and biophysics reports · 2026Article
- Hnf1aos1 as a Metabolic Coordinator of Hepatic Lipid Homeostasis and Feedback Control.Non-coding RNA · 2026Article
- Exercise Impacts Liver Disease: Balancing Metabolic and Immune Homeostasis.International journal of biological sciences · 2026Review
- Western Diet Induces Changes in Gene Expression in Multiple Tissues During Early Insulin Resistance and Glucose Intolerance in Male C57BL/6 Mice.Current issues in molecular biology · 2025Article
- PPARγ, a key modulator of metabolic reprogramming, stemness and chemoresistance associated with retrodifferentiation in human hepatocellular carcinomas.Cell death & disease · 2025Article
- Hepatocyte nuclear factors dynamically regulate triglyceride metabolic reprogramming in metabolic dysfunction-associated steatotic liver disease: Mechanisms and implications.World journal of hepatology · 2025Review
- Genome-wide interaction study with body mass index identifies CYP7A1 and GIPR as genetic modulators of metabolic dysfunction-associated steatotic liver disease.Clinical and molecular hepatology · 2025Article
- Immunometabolic Targets in CD8Liver cancer · 2025Review
- Deciphering the roles of neddylation modification in hepatocellular carcinoma: Molecular mechanisms and targeted therapeutics.Genes & diseases · 2025Review
- Tripartite motif 8 promotes the progression of hepatocellular carcinoma via mediating ubiquitination of HNF1α.Cell death & disease · 2024Article
- Dual function of activated PPARγ by ligands on tumor growth and immunotherapy.Medical oncology (Northwood, London, England) · 2024Review
- Identification of PPAR-related differentially expressed genes liver hepatocellular carcinoma and construction of a prognostic model based on data analysis and molecular docking.Journal of cellular and molecular medicine · 2024Article
- Article
- Sortilin-induced lipid accumulation and atherogenesis are suppressed by HNF1b SUMOylation promoted by flavone ofJournal of Zhejiang University. Science. B · 2023Article
- Aberrant expression of cuproptosis‑related gene LIPT1 is associated with metabolic dysregulation of fatty acid and prognosis in hepatocellular carcinoma.Journal of cancer research and clinical oncology · 2023Article
- Swimming exercise ameliorates insulin resistance and nonalcoholic fatty liver by negatively regulating PPARγ transcriptional network in mice fed high fat diet.Molecular medicine (Cambridge, Mass.) · 2023Article
- Dominant-negative HNF1α mutant promotes liver steatosis and inflammation by regulating hepatic complement factor D.iScience · 2023Article
- Hepatocyte nuclear factor 1A suppresses innate immune response by inducing degradation of TBK1 to inhibit steatohepatitis.Genes & diseases · 2023Article
- Class 3 PI3K coactivates the circadian clock to promote rhythmic de novo purine synthesis.Nature cell biology · 2023Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Worldwide epidemics of metabolic diseases, including liver steatosis, are associated with an increased frequency of malignancies, showing the highest positive correlation for liver cancer. The heterogeneity of liver cancer represents a clinical challenge. In liver, the transcription factor PPARγ promotes metabolic adaptations of lipogenesis and aerobic glycolysis under the control of Akt2 activity, but the role of PPARγ in liver tumorigenesis is unknown. Here we have combined preclinical mouse models of liver cancer and genetic studies of a human liver biopsy atlas with the aim of identifying putative therapeutic targets in the context of liver steatosis and cancer. We have revealed a protumoral interaction of Akt2 signaling with hepatocyte nuclear factor 1α (HNF1α) and PPARγ, transcription factors that are master regulators of hepatocyte and adipocyte differentiation, respectively. Akt2 phosphorylates and inhibits HNF1α, thus relieving the suppression of hepatic PPARγ expression and promoting tumorigenesis. Finally, we observed that pharmacological inhibition of PPARγ is therapeutically effective in a preclinical murine model of steatosis-associated liver cancer. Taken together, our studies in humans and mice reveal that Akt2 controls hepatic tumorigenesis through crosstalk between HNF1α and PPARγ.
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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.