ArticleThe Journal of clinical investigation2023
Gluconeogenic enzyme PCK1 supports S-adenosylmethionine biosynthesis and promotes H3K9me3 modification to suppress hepatocellular carcinoma progression.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 55 citations in OpenAlex.
- S100A11 regulates hepatic cholesterol metabolism and promotes steatohepatitis via noncanonical SREBP2 signaling.The Journal of clinical investigation · 2026Article
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- Myeloid-SpecificbioRxiv : the preprint server for biology · 2026Article
- Hepatocyte estrogen-related receptor α modulates a gluconeogenic-epigenetic crosstalk counteracting MASLD/MASH progression.Experimental & molecular medicine · 2026Article
- Pck1 Deficiency Drives Mitochondrial Dysfunction and Cellular Senescence in Adipocytes.Aging cell · 2026Article
- Transcriptomic and metabolomic profiles reveal the functions of IGF-1 c.258 A > G synonymous mutation in milk fat content.Journal of advanced research · 2026Article
- Metabolic reprogramming in cancer: dysregulation of glucose, lipid, and amino acid pathways and therapeutic opportunities.Molecular biomedicine · 2026Review
- Amino acid metabolic regulatory network in tumor immune escape: mechanistic exploration and intervention directions.Frontiers in immunology · 2026Review
- One-carbon metabolism in cancer immunity: T-cell fitness, epigenetic programming, and therapeutic opportunities.Frontiers in immunology · 2026Review
- Dual-pathway mechanism of vanadium-induced hepatotoxicity in ducks: Synergistic crosstalk between glucose homeostasis disruption and NADH/FSP1/COQ10 axis-driven ferroptosis.International journal of biological sciences · 2026Article
- PCK1 attenuates intrahepatic cholangiocarcinoma progression by suppressing lactate accumulation and PI3K-AKT signaling.Functional & integrative genomics · 2025Article
- Suppressing the OTUD7A/KDM5B/GABPA axis enhances the sensitivity of cisplatin through inducing ferroptosis in KRAS-mutant LUAD.Cell death & disease · 2025Article
- S-adenosylmethionine enhances anti-PD-1 efficacy in uveal melanoma by targeting EZH2.Discover oncology · 2025Article
- Comparative analysis of S100A10 and S100A11 in MASLD and hepatic cancer development revealed a tumor suppressive role for S100A10.Cell death & disease · 2025Article
- Simvastatin overcomes the pPCK1-pLDHA-SPRINGlac axis-mediated ferroptosis and chemo-immunotherapy resistance in AKT-hyperactivated intrahepatic cholangiocarcinoma.Cancer communications (London, England) · 2025Article
- Inhibition of liver cancer cell growth by metabolites S-adenosylmethionine and nicotinic acid originating from liver progenitor cells.Journal of gastroenterology · 2025Article
- Sulfide regulation and catabolism in health and disease.Signal transduction and targeted therapy · 2025Review
- BRD1 deficiency affects SREBF1-related lipid metabolism through regulating H3K9ac/H3K9me3 transition to inhibit HCC progression.Cell death & disease · 2025Article
- Article
- Metabolic reprogramming of glucose: the metabolic basis for the occurrence and development of hepatocellular carcinoma.Frontiers in oncology · 2025Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Deciphering the crosstalk between metabolic reprogramming and epigenetic regulation is a promising strategy for cancer therapy. In this study, we discovered that the gluconeogenic enzyme PCK1 fueled the generation of S-adenosylmethionine (SAM) through the serine synthesis pathway. The methyltransferase SUV39H1 catalyzed SAM, which served as a methyl donor to support H3K9me3 modification, leading to the suppression of the oncogene S100A11. Mechanistically, PCK1 deficiency-induced oncogenic activation of S100A11 was due to its interaction with AKT1, which upregulated PI3K/AKT signaling. Intriguingly, the progression of hepatocellular carcinoma (HCC) driven by PCK1 deficiency was suppressed by SAM supplement or S100A11 KO in vivo and in vitro. These findings reveal the availability of the key metabolite SAM as a bridge connecting the gluconeogenic enzyme PCK1 and H3K9 trimethylation in attenuating HCC progression, thus suggesting a potential therapeutic strategy against HCC.
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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.