ArticleCell death & disease2022
S1PR1 induces metabolic reprogramming of ceramide in vascular endothelial cells, affecting hepatocellular carcinoma angiogenesis and progression.
Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 44 citations in OpenAlex.
- Sphingolipid homeostasis and dysregulation in liver function and disease.Life metabolism · 2026Review
- Self-Assembly of Stimuli-Responsive Peptide Enhances Therapeutics by Specifically Disrupting Hepatocellular Carcinoma Lysosomes In Vivo.Advanced materials (Deerfield Beach, Fla.) · 2026Article
- Multi-omics integration model of exosome metabolomics and PD-1/PD-L1 expression for early prediction of immunotherapy efficacy in advanced liver cancer.Scientific reports · 2026Article
- Targeting tumor-associated G-protein coupled receptors: beyond single-axis inhibition toward multidimensional regulation.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Reprogrammed Lipid Metabolism as a Gatekeeper of Hepatocarcinogenesis: from Enzyme Regulation to Precision Therapy.Current oncology reports · 2026Review
- Fractional carbon dioxide laser-induced photothermal activation of mesenchymal stem cell-derived exosomes accelerates diabetic wound healing by enhancing angiogenesis.World journal of diabetes · 2026Article
- Article
- GBA3 as a regulator of sphingolipid metabolism in the progression of hepatocellular carcinoma.Journal of gastrointestinal oncology · 2025Article
- AURKA promotes angiogenesis in uveal melanoma via activation of the JAK2/STAT3/VEGFA signaling pathway.Cancer cell international · 2025Article
- Transcriptomics, lipidomics, and single-nucleus RNA sequencing integration: exploring sphingolipids in MASH-HCC progression.Cell & bioscience · 2025Article
- Benign non-immune cells in tumor microenvironment.Frontiers in immunology · 2025Review
- Multi-omics dissection of tumor microenvironment-mediated drug resistance: mechanisms and therapeutic reprogramming.Frontiers in pharmacology · 2025Review
- Critical Roles of the Sphingolipid Metabolic Pathway in Liver Regeneration, Hepatocellular Carcinoma Progression and Therapy.Cancers · 2024Review
- Article
- Advances in Targeted Drug Resistance Associated with Dysregulation of Lipid Metabolism in Hepatocellular Carcinoma.Journal of hepatocellular carcinoma · 2024Review
- Defining the cellular complexity of the zebrafish bipotential gonad.Biology of reproduction · 2023Article
- Feline mammary carcinoma-derived extracellular vesicle promotes liver metastasis via sphingosine kinase-1-mediated premetastatic niche formation.Laboratory animal research · 2023Article
- S1P/S1PR signaling pathway advancements in autoimmune diseases.Biomolecules & biomedicine · 2023Review
- Mechanisms and therapeutic strategies to combat the recurrence and progression of hepatocellular carcinoma after thermal ablation.Journal of interventional medicine · 2023Article
- CrMP-Sol database: classification, bioinformatic analyses and comparison of cancer-related membrane proteins and their water-soluble variant designs.BMC bioinformatics · 2023Article
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Angiogenesis is a fundamental process underlying the occurrence, growth and metastasis of hepatocellular carcinoma (HCC), a prevalent tumour type with an extremely poor prognosis due to abundant vasculature. However, the underlying mechanism of angiogenesis in HCC remains largely unknown. Herein, we found that sphingosine-1-phosphate receptor 1 (S1PR1) plays an important role in HCC angiogenesis. S1PR1 was found to be selectively and highly expressed in the blood vessels of HCC tissues compared with those of paratumour tissues. Functionally, high expression of S1PR1 in endothelial cells (ECs) promoted angiogenesis and progression of HCC in vitro and in vivo. Mechanistically, proangiogenic factors (S1P, IL-6, VEGFA) in conditioned medium from HCC cells induced the upregulation of S1PR1 in ECs via the phosphorylation of STAT3 at Y705. Further study also revealed that S1PR1 promotes angiogenesis by decreasing ceramide levels via CerS3 downregulation. Interestingly, we demonstrated that S1PR1 downregulates CerS3 by inducing CerS6 translocation into the nucleus to inhibit CerS3 at the transcriptional level in ECs. In addition, we found that a high concentration of Lenvatinib significantly downregulated the expression of S1PR1 and obviously enhanced S1PR1 knockdown-mediated angiogenesis inhibition, indicating that S1PR1 may be a target by which Lenvatinib combats angiogenesis in HCC. Thus, S1PR1 may be an important target for suppressing angiogenesis in HCC, and inhibiting S1PR1 is a promising approach to antitumor therapy in HCC.
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