ArticleCancers2019
HMGCS2 Mediates Ketone Production and Regulates the Proliferation and Metastasis of Hepatocellular Carcinoma.
Article in Cancers, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed.
- Gestational Ketosis Compromises Nephron Endowment and Long-Term Kidney Function in Offspring.Journal of the American Society of Nephrology : JASN · 2026Article
- Gut Microbiota, Immunity, and Metabolism in the Progression From Chronic Liver Disease to Hepatocellular Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- MicroRNA isomiRs reveal novel pathways linked to disease activity and fibrosis in MASLD.Clinical and molecular hepatology · 2026Article
- SIRT3 Regulates HMGCS2 Deacetylation and Influences Cholangiocarcinoma Progression via the Metabolism of Ketone Bodies.Human mutation · 2026Article
- Gut microbiota in hepatocellular carcinoma immunotherapy: immune microenvironment remodeling and gut microbiota modification.Gut microbes · 2025Review
- Article
- Not Just an Alternative Energy Source: Diverse Biological Functions of Ketone Bodies and Relevance of HMGCS2 to Health and Disease.Biomolecules · 2025Review
- Ketogenic diet and cancer: multidimensional exploration and research.Science China. Life sciences · 2025Review
- Deciphering Colorectal Cancer-Hepatocyte Interactions: A Multiomics Platform for Interrogation of Metabolic Crosstalk in the Liver-Tumor Microenvironment.International journal of molecular sciences · 2025Article
- Discovery of PPAR Alpha Lipid Pathway Modulators That Do Not Bind Directly to the Receptor as Potential Anti-Cancer Compounds.International journal of molecular sciences · 2025Article
- Comprehensive Overview of Ketone Bodies in Cancer Metabolism: Mechanisms and Application.Biomedicines · 2025Review
- Mitochondrial Gene Scoring System: Predicting Prognosis and Precision Therapy for TACE Non-Response in Hepatocellular Carcinoma Patients.Journal of Cancer · 2025Article
- Deciphering Colorectal Cancer-Hepatocyte Interactions: A Multiomic Platform for Interrogation of Metabolic Crosstalk in the Liver-Tumor Microenvironment.bioRxiv : the preprint server for biology · 2024Article
- Article
- Integrative analysis of bulk and single-cell transcriptomic data reveals novel insights into lipid metabolism and prognostic factors in hepatocellular carcinoma.Discover oncology · 2024Article
- Ketogenic diet reshapes cancer metabolism through lysine β-hydroxybutyrylation.Nature metabolism · 2024Article
- Article
- BET inhibition decreases HMGCS2 and sensitizes resistant pancreatic tumors to gemcitabine.Cancer letters · 2024Article
- Targeting ketone body metabolism to treat fatty liver disease.Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques · 2024Review
- Human Milk Supports Robust Intestinal Organoid Growth, Differentiation, and Homeostatic Cytokine Production.Gastro hep advances · 2024Article
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
Hepatocellular carcinoma (HCC) is the most common primary malignant tumor worldwide; however, the traditional therapeutic approaches and survival rates are still limited. To improve current therapies, it is necessary to investigate the molecular mechanisms underlying liver cancer and to identify potential therapeutic targets. The aims of this study were to verify the mechanisms and therapeutic potential of the ketogenesis rate-limiting enzyme 3-Hydroxymethylglutaryl-CoA synthase 2 (HMGCS2) in HCC. Immunohistochemical staining of human liver disease tissue arrays showed that HMGCS2 is abundantly expressed in normal liver tissues but is downregulated in cirrhosis and HCC tissues. In HCC patients, lower HMGCS2 expression was correlated with higher pathological grades and clinical stages. In our investigation of the molecular mechanisms of HMGCS2 in HCC, we showed that knockdown of HMGCS2 decreased ketone production, which promoted cell proliferation, cell migration, and xenograft tumorigenesis by enhancing c-Myc/cyclinD1 and EMT signaling and by suppressing the caspase-dependent apoptosis pathway. Ketone body treatment reduced the proliferation- and migration-promoting effects of HMGCS2 knockdown in cells. In contrast, HMGCS2 overexpression increased the intracellular ketone level and inhibited cell proliferation, cell migration, and xenograft tumorigenesis. Finally, ketogenic diet administration significantly inhibited liver cancer cell growth in mice. Our studies highlight the potential therapeutic strategy of targeting HMGCS2-mediated ketogenesis in liver cancer.
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