ArticleNature communications2020
HNF4α regulates sulfur amino acid metabolism and confers sensitivity to methionine restriction in liver cancer.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed, 123 citations in OpenAlex.
- Vitamin BNature communications · 2026Article
- Food Functional Factors and Nutritional Health.Nutrients · 2026Article
- Role of methionine metabolism in cancer: recent advances in molecular mechanisms and therapeutic implications.Experimental hematology & oncology · 2026Review
- Unexpected Microbial and Genetic Diversity in the Gut of Chinese Giant Salamander.Integrative zoology · 2026Article
- Activation of methionine metabolism mediated by HNF4α confers ferroptosis resistance in hepatocellular carcinoma.Cell death discovery · 2026Article
- PPARγ-dependent and -independent regulation of methionine metabolism by diet-induced obesity and fasting in male mice.bioRxiv : the preprint server for biology · 2026Article
- Methionine restriction for cancer therapy: From preclinical studies to clinical trials.Cancer pathogenesis and therapy · 2026Review
- Integrated machine learning and bioinformatic analyses constructed a sulfur metabolism-related breast cancer risk model and identified heat-shock protein A9 as a potential therapeutic target for human breast cancer.Discover oncology · 2026Article
- PPARγ-dependent and -independent regulation of genes involved in hepatic methionine cycle in fasted or diet-induced obese mice.PloS one · 2026Article
- Cysteine Restriction Induces Ferroptosis Depending on theGastro hep advances · 2026Article
- Targeting CREB3L2-mediated lipid metabolism overcomes lenvatinib resistance and attenuates the progression of hepatocellular carcinoma.Cell death & disease · 2025Article
- Vitamin BResearch square · 2025Article
- Metabolic dysfunction-associated steatohepatitis reduces hepatic HRedox biology · 2025Article
- Targeting macro- and micro-nutrient regulation of HNeurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- Hepatocyte nuclear factor 4-Alpha: a key regulator in liver carcinogenesis.Cellular oncology (Dordrecht, Netherlands) · 2025Review
- Role of amino acids in the regulation of hepatic gluconeogenesis and lipogenesis in metabolic dysfunctionassociated steatotic liver disease.Clinical and molecular hepatology · 2025Review
- Relationship between plasma homocysteine and clinical grading of varicocele.Asian journal of andrology · 2025Article
- Cysteine depletion triggers adipose tissue thermogenesis and weight loss.Nature metabolism · 2025Article
- Sugar and Free Amino Acid Contents in Winter Wheat Flour Under Fusarium Head Blight Treatment and Natural Infection.Plants (Basel, Switzerland) · 2025Article
- Methionine Dependency and Restriction in Cancer: Exploring the Pathogenic Function and Therapeutic Potential.Pharmaceuticals (Basel, Switzerland) · 2025Review
14 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 3 institutions in 3 countries.
Funding
Abstract
Methionine restriction, a dietary regimen that protects against metabolic diseases and aging, represses cancer growth and improves cancer therapy. However, the response of different cancer cells to this nutritional manipulation is highly variable, and the molecular determinants of this heterogeneity remain poorly understood. Here we report that hepatocyte nuclear factor 4α (HNF4α) dictates the sensitivity of liver cancer to methionine restriction. We show that hepatic sulfur amino acid (SAA) metabolism is under transcriptional control of HNF4α. Knocking down HNF4α or SAA enzymes in HNF4α-positive epithelial liver cancer lines impairs SAA metabolism, increases resistance to methionine restriction or sorafenib, promotes epithelial-mesenchymal transition, and induces cell migration. Conversely, genetic or metabolic restoration of the transsulfuration pathway in SAA metabolism significantly alleviates the outcomes induced by HNF4α deficiency in liver cancer cells. Our study identifies HNF4α as a regulator of hepatic SAA metabolism that regulates the sensitivity of liver cancer to methionine restriction.
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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.