ArticleOncotarget2018
Targeting the mevalonate pathway is a novel therapeutic approach to inhibit oncogenic FoxM1 transcription factor in human hepatocellular carcinoma.
Article in Oncotarget, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 36 citations in OpenAlex.
- Repurposing statins for choriocarcinoma: targeting the mevalonate pathway to disrupt mechanosignaling and overcome therapeutic resistance.Clinical & experimental metastasis · 2026Review
- The oncogenic role of FOXM1 in hepatocellular carcinoma: molecular mechanisms, clinical significance, and therapeutic potentials.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Mechanism and therapeutic potential of liver injury induced by cholesterol-associated proteins.Frontiers in pharmacology · 2025Review
- Knockouts ofiScience · 2024Article
- Novel FOXM1 inhibitor STL001 sensitizes human cancers to a broad-spectrum of cancer therapies.Cell death discovery · 2024Article
- Dysregulated cholesterol regulatory genes in hepatocellular carcinoma.European journal of medical research · 2023Review
- Clinical Significance of Apurinic/Apyrimidinic Endodeoxyribonuclease 1 and MicroRNA Axis in Hepatocellular Carcinoma.Journal of clinical and translational hepatology · 2023Article
- Caffeine Supplementation and FOXM1 Inhibition Enhance the Antitumor Effect of Statins in Neuroblastoma.Cancer research · 2023Article
- Current trends and future prospects of drug repositioning in gastrointestinal oncology.Frontiers in pharmacology · 2023Review
- Methionine regulates self-renewal, pluripotency, and cell death of GIC through cholesterol-rRNA axis.BMC cancer · 2022Article
- Hepatic transcriptome profiling reveals early signatures associated with disease transition from non-alcoholic steatosis to steatohepatitis.Liver research (Beijing, China) · 2022Article
- Identification of prognostic long non-coding RNA signature with potential drugs in hepatocellular carcinoma.Aging · 2021Article
- Loss of ULK1 Attenuates Cholesterogenic Gene Expression in Mammalian Hepatic Cells.Frontiers in cell and developmental biology · 2020Article
- Targeting SREBP-2-Regulated Mevalonate Metabolism for Cancer Therapy.Frontiers in oncology · 2020Review
- Emerging risk factors for nonalcoholic fatty liver disease associated hepatocellular carcinoma.Hepatoma research · 2020Article
- Forkhead Box M1 Transcription Factor Drives Liver Inflammation Linking to Hepatocarcinogenesis in Mice.Cellular and molecular gastroenterology and hepatology · 2020Observational
- A high-cholesterol diet promotes steatohepatitis and liver tumorigenesis in HCV core gene transgenic mice.Archives of toxicology · 2019Article
- MiR-216b suppresses cell proliferation, migration, invasion, and epithelial-mesenchymal transition by regulating FOXM1 expression in human non-small cell lung cancer.OncoTargets and therapy · 2019Article
- Emodin Sensitizes Hepatocellular Carcinoma Cells to the Anti-Cancer Effect of Sorafenib through Suppression of Cholesterol Metabolism.International journal of molecular sciences · 2018Article
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dysregulation of cell metabolism is a hallmark of cancer. The mevalonate pathway in lipid metabolism has been implicated as a potential target of cancer therapy for hepatocellular carcinoma (HCC). The role of the Forkhead Box M1 (FoxM1) transcription factor in HCC development has been well documented, however, its involvement in cancer metabolism of HCC has not been fully determined. Here, we hypothesized that FoxM1 is involved in the mevalonate pathway of cholesterol biosynthesis in HCC. Inhibition of the mevalonate pathway by statins, inhibitors of 3-hydroxy-3-methylglutaryl CoA reductase (HMGCR), resulted in reduced expression of FoxM1 and increased cell death in human hepatoma cells. Re-exposure of mevalonate, a product of HMGCR, restored these effects. Likewise, knockdown of HMGCR reduced FoxM1 expression, indicating that FoxM1 expression was regulated by the mevalonate pathway in HCC. Mechanistically, protein geranylgeranylation was found to be responsible for FoxM1 expression and geranylgeranylated proteins, including RhoA, Rac1 or Cdc42, were shown to be involved in this process. In surgically resected human HCC tissues, the gene expression of
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