ArticleJournal of cellular and molecular medicine2021
ATP citrate lyase inhibitor triggers endoplasmic reticulum stress to induce hepatocellular carcinoma cell apoptosis via p-eIF2α/ATF4/CHOP axis.
Article in Journal of cellular and molecular medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 44 citations in OpenAlex.
- Emerging roles of ATP citrate lyase in kidney diseases: from pathogenic driver to therapeutic target.Renal failure · 2026Review
- New insights into the ACLY-mediated metabolic and epigenetic interplay in macrophages.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- Research progress on ATP-citrate lyase and its inhibitors: a metabolic-epigenetic perspective.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- Advances in Lipid Metabolism Reprogramming in Hepatocellular Carcinoma.Journal of clinical and translational hepatology · 2026Review
- Unveiling the antibacterial activity and mechanisms of BMS-303141 against Staphylococcus aureus.BMC microbiology · 2026Article
- De Novo Lipogenesis in Clear Cell Renal Cell Carcinoma: Mechanistic Insights and Therapeutic Implications.International journal of molecular sciences · 2026Review
- Metabolic reprogramming in cancer: signaling pathways and therapeutic targets.Molecular cancer · 2026Review
- Metabolic Reprogramming-Targeted Therapeutic Strategies in Primary Liver Cancer: A Bibliometric and Visualized Analysis.Journal of hepatocellular carcinoma · 2026Article
- Endoplasmic reticulum stress-mediated programmed cell death in the tumor microenvironment.Cell death discovery · 2025Review
- Dendritic cells: understanding ontogeny, subsets, functions, and their clinical applications.Molecular biomedicine · 2025Review
- Review
- Role of ATP citrate lyase and its complementary partner on fatty acid synthesis in gastric cancer.Scientific reports · 2024Article
- Histone lactylation drives CD8Nature immunology · 2024Article
- Chalcomoracin promotes apoptosis and endoplasmic reticulum stress in hepatocellular carcinoma cells.The Journal of antibiotics · 2024Article
- The role of DGAT1 and DGAT2 in regulating tumor cell growth and their potential clinical implications.Journal of translational medicine · 2024Review
- Role ofQuantitative biology (Beijing, China) · 2024Article
- Advances in Targeted Drug Resistance Associated with Dysregulation of Lipid Metabolism in Hepatocellular Carcinoma.Journal of hepatocellular carcinoma · 2024Review
- Radiogenomic landscape: Assessment of specific phagocytosis regulators in lower-grade gliomas.Experimental biology and medicine (Maywood, N.J.) · 2023Article
- Activation of ACLY by SEC63 deploys metabolic reprogramming to facilitate hepatocellular carcinoma metastasis upon endoplasmic reticulum stress.Journal of experimental & clinical cancer research : CR · 2023Article
- Identification of glutamyl-prolyl-tRNA synthetase as a new therapeutic target in hepatocellular carcinoma via a novel bioinformatic approach.Journal of gastrointestinal oncology · 2023Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
ATP citrate lyase (ACLY), a key enzyme in the metabolic reprogramming of many cancers, is widely expressed in various mammalian tissues. This study aimed to evaluate the effects and mechanisms of ACLY and its inhibitor BMS-303141 on hepatocellular carcinoma (HCC). In this study, ACLY was highly expressed in HCC tissues, especially in HepG2 and Huh7 cells, but was down-regulated in Hep3B and HCC-LM3 cells. Besides, ACLY knockdown inhibited HepG2 proliferation and clone formation, while opposite result was noticed in HCC-LM3 cells with ACLY overexpression. Moreover, ACLY knockdown impeded the migration and invasion abilities of HepG2 cells. Similarly, BMS-303141 suppressed HepG2 and Huh-7 cell proliferation. The p-eIF2α, ATF4, CHOP p-IRE1α, sXBP1 and p-PERK were activated in HepG2 cells stimulated by BMS-303141. In cells where ER stress was induced, ATF4 was involved in BMS-303141-mediated cell death procession, and ATF4 knockdown reduced HCC cell apoptosis stimulated by BMS-303141. In a mouse xenograft model, combined treatment with BMS-303141 and sorafenib reduced HepG2 tumour volume and weight. In addition, ACLY expression was associated with HCC metastasis and tumour-node-metastases staging. Survival analysis and Cox proportional hazards regression model showed that overall survival was lower in HCC patients with high ACLY expression; AFP level, TNM staging, tumour size and ACLY expression level were independent risk factors affecting their overall survival. In conclusion, ACLY might represent a promising target in which BMS-303141 could induce ER stress and activate p-eIF2α/ATF4/CHOP axis to promote apoptosis of HCC cells, and synergized with sorafenib to enhance the efficacy of HCC treatment.
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