ArticleOncogenesis2022
Ablation of sphingosine kinase 2 suppresses fatty liver-associated hepatocellular carcinoma via downregulation of ceramide transfer protein.
Article in Oncogenesis, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
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The trial behind it
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Who cites it
15 citing papers in PubMed, 26 citations in OpenAlex.
- Sphingolipid homeostasis and dysregulation in liver function and disease.Life metabolism · 2026Review
- An update on schistosomicide and tumoricide in the future: arachidonic acid.Lipids in health and disease · 2025Review
- Molecular network of metabolic reprogramming and precision diagnosis and treatment of hepatocellular carcinoma.Biomarker research · 2025Review
- An endothelial SOX18-mevalonate pathway axis enables repurposing of statins for infantile hemangioma.The Journal of clinical investigation · 2025Article
- Restoring metabolic flexibility: targeting organelle interaction networks in the pathogenesis and therapy of MASLD.Frontiers in cell and developmental biology · 2025Review
- Mechanisms and potential therapeutic targets of SphK1 and SphK2 in hepatocellular carcinoma.Frontiers in medicine · 2025Review
- Exploring the role of alternative lengthening of telomere-related genes in diagnostic modeling for non-alcoholic fatty liver disease.Scientific reports · 2024Article
- Sphingosine kinase 2 (SphK2) depletion alters redox metabolism and enhances inflammation in a diet-induced MASH mouse model.Hepatology communications · 2024Article
- Sphingosine kinase 2 and p62 regulation are determinants of sexual dimorphism in hepatocellular carcinoma.Molecular metabolism · 2024Article
- Critical Roles of the Sphingolipid Metabolic Pathway in Liver Regeneration, Hepatocellular Carcinoma Progression and Therapy.Cancers · 2024Review
- Identification of pre-diagnostic lipid sets associated with liver cancer risk using untargeted lipidomics and chemical set analysis: A nested case-control study within the ATBC cohort.International journal of cancer · 2024Article
- Targeting the SphK1/S1P/PFKFB3 axis suppresses hepatocellular carcinoma progression by disrupting glycolytic energy supply that drives tumor angiogenesis.Journal of translational medicine · 2024Article
- Integrative roles of sphingosine kinase in liver pathophysiology.Toxicological research · 2023Review
- Metabolic Reprogramming of HCC: A New Microenvironment for Immune Responses.International journal of molecular sciences · 2023Review
- Mechanisms of Arachidonic Acid In Vitro Tumoricidal Impact.Molecules (Basel, Switzerland) · 2023Article
Corrections and comments
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Authors and funding
18 authors at 3 institutions in 2 countries.
Funding
Abstract
Hepatocellular carcinoma (HCC) accounts for 90% of primary liver cancer, the third leading cause of cancer-associated death worldwide. With the increasing prevalence of metabolic conditions, non-alcoholic fatty liver disease (NAFLD) is emerging as the fastest-growing HCC risk factor, and it imposes an additional layer of difficulty in HCC management. Dysregulated hepatic lipids are generally believed to constitute a deleterious environment cultivating the development of NAFLD-associated HCC. However, exactly which lipids or lipid regulators drive this process remains elusive. We report herein that sphingosine kinase 2 (SphK2), a key sphingolipid metabolic enzyme, plays a critical role in NAFLD-associated HCC. Ablation of Sphk2 suppressed HCC development in NAFLD livers via inhibition of hepatocyte proliferation both in vivo and in vitro. Mechanistically, SphK2 deficiency led to downregulation of ceramide transfer protein (CERT) that, in turn, decreased the ratio of pro-cancer sphingomyelin (SM) to anti-cancer ceramide. Overexpression of CERT restored hepatocyte proliferation, colony growth and cell cycle progression. In conclusion, the current study demonstrates that SphK2 is an essential lipid regulator in NAFLD-associated HCC, providing experimental evidence to support clinical trials of SphK2 inhibitors as systemic therapies against 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.