ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2024
CSN6-SPOP-HMGCS1 Axis Promotes Hepatocellular Carcinoma Progression via YAP1 Activation.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
30 citing papers in PubMed, 28 citations in OpenAlex.
- Glutamine-driven metabolic reprogramming promotes CAR-T cell function through mTOR-SREBP2 mediated HMGCS1 upregulation in ovarian cancer.Journal of translational medicine · 2025Trial
- Not only as a Cullin3 ligase adaptor, SPOP may also act as a molecular bridge.Genes & diseases · 2027Review
- The Crosstalk Between YAP/TAZ and Cancer Metabolism: From Mechanistic Insights to Drug Discovery.International journal of molecular sciences · 2026Review
- Imaging mass cytometry reveals novel cellular neighborhoods for predicting the prognosis of nonalcoholic fatty liver disease-associated hepatocellular carcinoma.Cancer cell international · 2026Article
- SPOP-mediated K27-linked non-degradative ubiquitination of KCNN3 suppressing HCC progression via the CTCF-SATB1 axis.Cell death & disease · 2026Article
- The role of e3 ubiquitin ligases and deubiquitinating enzymes in hepatocellular carcinoma.Cell biology and toxicology · 2026Review
- Molecular insights for the tumor suppressor role of SPOP in prostate cancer.Biochimica et biophysica acta. Reviews on cancer · 2026Review
- Mevalonate pathway in pancreatic ductal adenocarcinoma: Mechanisms driving metabolic and cellular plasticity.Cancer pathogenesis and therapy · 2026Review
- ZOMES: expanding roles of the PCI complexes from protein metabolism to drug discovery.npj metabolic health and disease · 2026Article
- Single-cell mapping of cholesterol metabolism reveals FDPS as a therapeutic vulnerability in hepatocellular carcinoma.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- CSN6 Promotes Pancreatic Cancer Progression and Gemcitabine Resistance via Antagonizing DCAF1-Mediated Ubiquitination of NPM1.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- RhoE downregulation leads to enhanced cholesterol biosynthesis and sorafenib resistance in hepatocellular carcinoma.The Journal of biological chemistry · 2025Article
- Molecular network of metabolic reprogramming and precision diagnosis and treatment of hepatocellular carcinoma.Biomarker research · 2025Review
- Bone marrow mesenchymal stem cell-derived exosomes attenuate hepatic stellate cell activation through miR-223-3p-mediated mitophagy.BMC medical genomics · 2025Article
- Spatial Proteomic Analysis Highlights Molecular Reprogramming in Optic Nerve Invasive Retinoblastoma.Investigative ophthalmology & visual science · 2025Article
- RPL6 Interacts with HMGCS1 to Stabilize HIF-1α by Promoting Cholesterol Production in Hepatocellular Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- OVOL1 Promotes Proliferation and Metastasis of Non-Small Cell Lung Cancer by Regulating APOE-Mediated Cholesterol Metabolism.Journal of cellular and molecular medicine · 2025Article
- Review of roles of RNA-binding proteins on NAFLD and the related pharmaceutical measures.Biomolecules & biomedicine · 2025Review
- CDK4/6-mediated phosphorylation of DUB3 promotes YAP1 stability and hepatocellular carcinoma progression.Cell death discovery · 2025Article
- Lactobacillus acidophilus potentiates oncolytic virotherapy through modulating gut microbiota homeostasis in hepatocellular carcinoma.Nature communications · 2025Article
Corrections and comments
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Authors and funding
25 authors at 4 institutions in 1 country.
Funding
Abstract
Cholesterol metabolism has important roles in maintaining membrane integrity and countering the development of diseases such as obesity and cancers. Cancer cells sustain cholesterol biogenesis for their proliferation and microenvironment reprograming even when sterols are abundant. However, efficacy of targeting cholesterol metabolism for cancer treatment is always compromised. Here it is shown that CSN6 is elevated in HCC and is a positive regulator of hydroxymethylglutaryl-CoA synthase 1 (HMGCS1) of mevalonate (MVA) pathway to promote tumorigenesis. Mechanistically, CSN6 antagonizes speckle-type POZ protein (SPOP) ubiquitin ligase to stabilize HMGCS1, which in turn activates YAP1 to promote tumor growth. In orthotopic liver cancer models, targeting CSN6 and HMGCS1 hinders tumor growth in both normal and high fat diet. Significantly, HMGCS1 depletion improves YAP inhibitor efficacy in patient derived xenograft models. The results identify a CSN6-HMGCS1-YAP1 axis mediating tumor outgrowth in HCC and propose a therapeutic strategy of targeting non-alcoholic fatty liver diseases- associated HCC.
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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.