ArticleMolecular therapy : the journal of the American Society of Gene Therapy2022
Sphingosine-1-phosphate transporter spinster homolog 2 is essential for iron-regulated metastasis of hepatocellular carcinoma.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 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, 43 citations in OpenAlex.
- SPNS2 exports sphingosine-1-phosphate and imports glucose.Nature communications · 2026Article
- Mechanosensitive calcium ion channels Piezo1: A therapeutic target in liver disease.Molecular therapy. Nucleic acids · 2025Review
- Targeting Annexin A2 to reactivate tumor-associated antigens presentation and relieve immune tolerance in liver cancer.Journal for immunotherapy of cancer · 2025Article
- Iron metabolism in a mouse model of hepatocellular carcinoma.Scientific reports · 2025Article
- Differentiating Liver Metastases from Primary Liver Cancer: A Retrospective Study of Imaging and Pathological Features in Patients with Histopathological Confirmation.Biomedicines · 2025Article
- Transferrin receptor uptakes iron from tumor-associated neutrophils to regulate invasion patterns of OSCC.Cancer immunology, immunotherapy : CII · 2025Article
- Lasso-Based Nomogram for Predicting Early Recurrence Following Radical Resection in Hepatocellular Carcinoma.Journal of hepatocellular carcinoma · 2025Article
- Low Indoleamine 2,3-Dioxygenase 1 Expression Enhances Dendritic Cells Response to Tumor Cells Against Hepatocellular Carcinoma.Journal of hepatocellular carcinoma · 2025Article
- Hepatic Arterial Infusion Chemotherapy Combined Apatinib/Camrelizumab for Recurrent Hepatocellular Carcinoma After Hepatectomy.Journal of hepatocellular carcinoma · 2025Article
- DNAJB1-PKAc Kinase Is Expressed in Young Patients with Pediatric Liver Cancers and Enhances Carcinogenic Pathways.Cancers · 2024Article
- Targeting Lipid Metabolism in Cancer Stem Cells for Anticancer Treatment.International journal of molecular sciences · 2024Review
- Spinster homolog 2 (SPNS2) deficiency drives endothelial cell senescence and vascular aging via promoting pyruvate metabolism mediated mitochondrial dysfunction.Cell communication and signaling : CCS · 2024Article
- A Novel Murine Model Enabling rAAV8-PC Gene Therapy for Severe Protein C Deficiency.International journal of molecular sciences · 2024Article
- Mitochondrial GCN5L1 acts as a novel regulator for iron homeostasis to promote sorafenib sensitivity in hepatocellular carcinoma.Journal of translational medicine · 2024Article
- Spinster Homologue 2 Expression Correlates With Improved Patient Survival in Hepatocellular Carcinoma Despite Association With Lymph-Angiogenesis.World journal of oncology · 2024Article
- METTL3 as a novel diagnosis and treatment biomarker and its association with glycolysis, cuproptosis and ceRNA in oesophageal carcinoma.Journal of cellular and molecular medicine · 2024Article
- Mechanisms of dihydromyricetin against hepatocellular carcinoma elucidated by network pharmacology combined with experimental validation.Pharmaceutical biology · 2023Article
- Adeno-Associated virus 8 delivers an immunomodulatory peptide to mouse liver more efficiently than to rat liver.PloS one · 2023Article
- UBA1 inhibition contributes radiosensitization of glioblastoma cellsFrontiers in pharmacology · 2023Article
- Adeno-associated virus vector-mediated gene therapy for the treatment of ovarian cancer: a literature review.Annals of translational medicine · 2022Review
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Authors and funding
13 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Iron dyshomeostasis is associated with hepatocellular carcinoma (HCC) development. However, the role of iron in HCC metastasis is unknown. This study aimed to elucidate the underlying mechanisms of iron's enhancement activity on HCC metastasis. In addition to the HCC cell lines and clinical samples in vitro, iron-deficient (ID) mouse models were generated using iron-free diet and transferrin receptor protein knockout, followed by administration of HCC tumors through either orthotopic or ectopic route. Clinical metastatic HCC samples showed significant ID status, accompanied by overexpression of sphingosine-1-phosphate transporter spinster homolog 2 (SPNS2). Mechanistically, ID increased SPNS2 expression, leading to HCC metastasis in both cell cultures and mouse models. ID not only altered the anti-tumor immunity, which was indicated by phenotypes of lymphatic subsets in the liver and lung of tumor-bearing mice, but also promoted HCC metastasis in a cancer cell autonomous manner through the SPNS2. Since germline knockout of globe SPNS2 showed significantly reduced HCC metastasis, we further developed hepatic-targeting recombinant adeno-associated virus vectors to knockdown SPNS2 expression and to inhibit iron-regulated HCC metastasis. Our observation indicates the role of iron in HCC pulmonary metastasis and suggests SPNS2 as a potential therapeutic target for the prevention of HCC pulmonary metastasis.
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