ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025
Targeting FDFT1 Reduces Cholesterol and Bile Acid Production and Delays Hepatocellular Carcinoma Progression Through the HNF4A/ALDOB/AKT1 Axis.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- SQLE as a potential diagnostic and prognostic biomarker for LIHC: a multi-cohort and spatial study.NPJ precision oncology · 2026Article
- Obesity-derived metabolites modulate anti-tumor immunity in the tumor microenvironment: from mechanisms to clinical applications.BMC medicine · 2026Review
- Research on zoledronic acid's synergistic improvement of intervertebral disc degeneration and osteoporosis by regulating inflammation matrix microenvironment.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- FDFT1 Acts as a Negative Regulator of Autophagy by Modulating AMPK-ULK1 Signaling in Hepatocellular Carcinoma Cells.Biomolecules & therapeutics · 2026Article
- Targeting ER lipid raft-associated 1 reveals a coordinated cholesterol-dependent vulnerability in hepatocellular carcinoma.Clinical and molecular hepatology · 2026Article
- Schwann Cell Synthesized Cholesterol Orchestrates Peripheral Nerve Regeneration via Structural and IGF1-Dependent Signaling Mechanisms.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Icaritin eliminates tumor-associated macrophages via STX16-dependent extracellular vesicle delivery of autophagosomes from hepatocellular carcinoma cells.Journal of experimental & clinical cancer research : CR · 2026Article
- L-Theanine ameliorates high-protein diet-associated hepatic glucose and lipid metabolic alterations by promoting fatty acid β-oxidation and suppressing lipid synthesis and gluconeogenesis in rats.Current research in food science · 2026Article
- Cholesterol metabolic rewiring shapes immune remodeling across hepatocarcinogenesis.Frontiers in immunology · 2026Review
- Combined vitamins D3 and K2 as potential modulators of multiple myeloma cell pathophysiology: transcriptomic and epigenetic effects under standard culture and bone marrow-like conditions.Frontiers in oncology · 2026Article
- "Top-down and Bottom-up" cholesterol-depleting biomimetic nanoparticle for enhancing sonodynamic therapy against hepatocellular carcinoma.Materials today. Bio · 2025Article
- Cholesterol metabolism and cancer: Molecular mechanisms, immune regulation and an epidemiological perspective (Review).International journal of molecular medicine · 2025Review
- Immune-related long noncoding RNAs in predicting the prognosis and immune landscape of intrahepatic cholangiocarcinoma: a bioinformatics analysis with experimental verification.Translational cancer research · 2025Article
- Study of mechanism of drug-induced liver injury caused by pyrethroid insecticides based on network toxicology and mendelian randomization.Toxicology research · 2025Article
- Transcriptomic analysis identifies key genes associated with nutrient deprivation responses in infectious bursal disease virus infection.BMC genomics · 2025Article
- Ginsenoside 20(S)-Rg3 upregulates SQLE to reprogram cholesterol metabolism of ovarian cancer cells.iScience · 2025Article
- Targeting FDFT1 Reduces Cholesterol and Bile Acid Production and Delays Hepatocellular Carcinoma Progression Through the HNF4A/ALDOB/AKT1 Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Valproic acid induces ferroptosis and suppresses the proliferation of MDA-MB-231 cells by targeting FDFT1.Frontiers in pharmacology · 2025Article
- The U-Shaped Association Between Remnant Cholesterol and Postoperative Survival in Hepatocellular Carcinoma: Development and Validation of an Interpretable Machine Learning Model.Journal of hepatocellular carcinoma · 2025Article
- Identification of FDFT1 and PGRMC1 as New Biomarkers in Nonalcoholic Steatohepatitis (NASH)-Related Hepatocellular Carcinoma by Deep Learning.Journal of hepatocellular carcinoma · 2025Article
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
Targeting cholesterol metabolism is a novel direction for tumor therapy. Unfortunately, the current use of statins for hepatocellular carcinoma (HCC) is controversial. Herein, farnesyl-diphosphate farnesyltransferase 1 (FDFT1) is identified as a novel target for treating HCC and a potential alternative to statins. Twenty-three key genes in cholesterol biosynthesis are screened, and FDFT1 is identified via public databases (The Cancer Genome Atlas, International Cancer Genome Consortium and Gene Expression Omnibus). Clinical samples reveal that FDFT1 is highly expressed in HCC tissues, and this phenotype is strongly associated with a poor prognosis. Functionally, FDFT1 knockdown inhibits the proliferation and metastasis of HCC cells and suppresses hepatocarcinogenesis in vitro and in vivo, whereas FDFT1 overexpression promotes HCC cell proliferation and metastasis. Mechanistically, FDFT1 downregulation decreases cholesterol and bile acid levels and then increases hepatocyte nuclear factor 4 alpha (HNF4A) transcriptional activity. Experiments indicate that HNF4A combines with the promoter of aldolase B (ALDOB) and promotes the ALDOB transcription and that ALDOB combines with AKT serine/threonine kinase 1 (AKT1) and inhibits AKT1 phosphorylation. Moreover, FDFT1 knockdown combined with AKT inhibitor (AZD5363) treatment shows remarkable therapeutic potential. FDFT1 inhibition reduces cholesterol and bile acid levels to delay HCC progression through the HNF4A/ALDOB/AKT1 axis. Thus, targeting FDFT1 may be a novel potential strategy for treating HCC.
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