ArticleJCI insight2023
Interfering with lipid metabolism through targeting CES1 sensitizes hepatocellular carcinoma for chemotherapy.
Article in JCI insight, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 41 citations in OpenAlex.
- The pivotal role of SCD1 in digestive cancers: Bridging lipid metabolic reprogramming and programmed cell death (Review).International journal of oncology · 2026Review
- Inhibiting menin attenuates high-fat diet-induced weight gain by limiting intestinal lipid absorption in mice.The Journal of clinical investigation · 2026Article
- StagX1, an isoquinolinone compound, selectively targets CES1-positive Ewing sarcoma cells as a potential therapeutic agent.Molecular therapy. Oncology · 2026Article
- Advances in Lipid Metabolism Reprogramming in Hepatocellular Carcinoma.Journal of clinical and translational hepatology · 2026Review
- Myeloid MMP14 couples extracellular proteolysis to inflammatory and metabolic remodeling during obesity.Cell reports · 2026Article
- Carboxylesterase 1 is a core metabolic vulnerability of platinum-resistant high-grade serous ovarian carcinoma.Journal of experimental & clinical cancer research : CR · 2026Article
- Article
- Unraveling the Link Between Azathioprine and Acute Pancreatitis: Integrating Network Toxicology, Machine Learning, and Mendelian Randomization.CPT: pharmacometrics & systems pharmacology · 2026Article
- Variant-to-Biomarker Integration and Mechanistic Validation Identify CES1 as a Copy Number-Linked Predictor of Radiotherapy Response in Rectal Cancer.Human mutation · 2026Article
- Macrophage-linked lipid metabolic signatures for HCC prognosis identified through integrated bulk and single-cell transcriptomics.Frontiers in immunology · 2026Article
- Triazine Thiols Decrease Apolipoprotein B Secretion From Hepatocytes Through Inhibition of Human Carboxylesterase 1.Cellular and molecular gastroenterology and hepatology · 2026Article
- Unraveling the YAP1-TGFβ1 axis: a key driver of androgen receptor loss in prostate cancer-associated fibroblasts.Journal of experimental & clinical cancer research : CR · 2025Article
- Discovery of lignans as the effective inhibitors of CES1A alleviate lipid droplets formation.Journal of enzyme inhibition and medicinal chemistry · 2025Article
- Anticancer Activity of Roburic Acid: In Vitro and In Silico Investigation.International journal of molecular sciences · 2025Article
- Functional regulation of macrophages by Ces1d-mediated lipid signaling in immunometabolism.Molecular metabolism · 2025Article
- Differential expression of capecitabine-related metabolic enzymes in hepatocellular carcinoma and its clinical value: a retrospective cohort study.Discover oncology · 2025Article
- Article
- Association between cancer-associated fibroblasts and prognosis of neoadjuvant chemoradiotherapy in esophageal squamous cell carcinoma: a bioinformatics analysis based on single-cell RNA sequencing.Cancer cell international · 2025Article
- Inflammation in cancer: therapeutic opportunities from new insights.Molecular cancer · 2025Review
- Carboxylesterase 1-mediated endocannabinoid metabolism in skin: role in melanoma progression in BRafCancer & metabolism · 2025Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Hepatocellular carcinoma (HCC) is the most common lethal form of liver cancer. Apart from surgical removal and transplantation, other treatments have not yet been well established for patients with HCC. In this study, we found that carboxylesterase 1 (CES1) is expressed at various levels in HCC. We further revealed that blockage of CES1 by pharmacological and genetical approaches leads to altered lipid profiles that are directly linked to impaired mitochondrial function. Mechanistically, lipidomic analyses indicated that lipid signaling molecules, including polyunsaturated fatty acids (PUFAs), which activate PPARα/γ, were dramatically reduced upon CES1 inhibition. As a result, the expression of SCD, a PPARα/γ target gene involved in tumor progression and chemoresistance, was significantly downregulated. Clinical analysis demonstrated a strong correlation between the protein levels of CES1 and SCD in HCC. Interference with lipid signaling by targeting the CES1-PPARα/γ-SCD axis sensitized HCC cells to cisplatin treatment. As a result, the growth of HCC xenograft tumors in NU/J mice was potently slowed by coadministration of cisplatin and CES1 inhibition. Our results, thus, suggest that CES1 is a promising therapeutic target for HCC treatment.
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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.