ArticleThe Journal of biological chemistry2016
TGF-β/SMAD3 Pathway Stimulates Sphingosine-1 Phosphate Receptor 3 Expression: IMPLICATION OF SPHINGOSINE-1 PHOSPHATE RECEPTOR 3 IN LUNG ADENOCARCINOMA PROGRESSION.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- Safety of S1P Modulators in Patients with Immune-Mediated Diseases: A Systematic Review and Meta-Analysis.Drug safety · 2021Pooled it
- Decoding the S1P-S1PR axis in cancer: Mechanisms, pathways and therapeutic horizons (Review).Biomedical reports · 2026Review
- Sphingosine-1-Phosphate Receptor 3 Confers Tumor Metastasis in Lung Cancer Resistant to Third-Generation EGFR Inhibitor.MedComm · 2026Article
- Sphingolipid metabolism dysregulation: A cause for lung cancer development, progression, and resistance to therapies.Chinese medical journal pulmonary and critical care medicine · 2025Review
- S1PR3 inhibition impairs cell cycle checkpoint via the AKT/WEE1 pathway in oral squamous cell carcinoma.Journal of translational medicine · 2025Article
- Targeting sphingosine 1-phosphate receptor 3 inhibits T-cell exhaustion and regulates recruitment of proinflammatory macrophages to improve antitumor efficacy of CAR-T cells against solid tumor.Journal for immunotherapy of cancer · 2023Article
- Inhibition of sphingosine-1-phosphate receptor 3 suppresses ATP-induced NLRP3 inflammasome activation in macrophagesFrontiers in immunology · 2023Article
- Targeting SPHK1/PBX1 Axis Induced Cell Cycle Arrest in Non-Small Cell Lung Cancer.International journal of molecular sciences · 2022Article
- [Research advances of the roles of sphingosine-1-phosphate in acute lung injury].Zhonghua shao shang yu chuang mian xiu fu za zhi · 2022Review
- Review
- Keep a Little Fire Burning-The Delicate Balance of Targeting Sphingosine-1-Phosphate in Cancer Immunity.International journal of molecular sciences · 2022Review
- Sphingolipid Metabolism and Signaling in Lung Cancer: A Potential Therapeutic Target.Journal of oncology · 2022Review
- Sphingolipid Metabolism in Glioblastoma and Metastatic Brain Tumors: A Review of Sphingomyelinases and Sphingosine-1-Phosphate.Biomolecules · 2020Review
- Lipid Phosphate Phosphatases and Cancer.Biomolecules · 2020Review
- Sphingosine-1-Phosphate: Its Pharmacological Regulation and the Treatment of Multiple Sclerosis: A Review Article.Biomedicines · 2020Review
- circ-FNTA accelerates proliferation and invasion of bladder cancer.Oncology letters · 2020Article
- Differential expression of S1P receptor subtypes in human bladder transitional cell carcinoma.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2019Article
- S1P/S1PR3 axis promotes aerobic glycolysis by YAP/c-MYC/PGAM1 axis in osteosarcoma.EBioMedicine · 2019Article
- The role of contextual signal TGF-β1 inducer of epithelial mesenchymal transition in metastatic lung adenocarcinoma patients with brain metastases: an update on its pathological significance and therapeutic potential.Contemporary oncology (Poznan, Poland) · 2019Review
- Roles of sphingosine-1-phosphate signaling in cancer.Cancer cell international · 2019Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Previously, we showed that levels of sphingosine-1 phosphate receptor 3 (S1PR3) are increased in a panel of cultured human lung adenocarcinoma cell lines, and that S1PR3-mediated signaling pathways regulate proliferation, soft agar growth, and invasion of human lung adenocarcinoma cells in vitro In the present study, we examine S1PR3 levels in human lung adenocarcinoma specimens. cDNA array and tumor microarray analysis shows that mRNA and protein levels of S1PR3 are significantly increased in human lung adenocarcinomas when compared with normal lung epithelial cells. Promoter analysis shows 16 candidate SMAD3 binding sites in the promoter region of S1PR3. ChIP indicates that TGF-β treatment stimulates the binding of SMAD3 to the promoter region of S1PR3. Luciferase reporter assay demonstrates that SMAD3 transactivates S1PR3 promoter. TGF-β stimulation or ectopic expression of TGF-β up-regulates S1PR3 levels in vitro and ex vivo Pharmacologic inhibition of TGF-β receptor or SMAD3 abrogates the TGF-β-stimulated S1PR3 up-regulation. Moreover, S1PR3 knockdown dramatically inhibits tumor growth and lung metastasis, whereas ectopic expression of S1PR3 promotes the growth of human lung adenocarcinoma cells in animals. Pharmacological inhibition of S1PR3 profoundly inhibits the growth of lung carcinoma in mice. Our studies suggest that levels of S1PR3 are up-regulated in human lung adenocarcinomas, at least in part due to the TGF-β/SMAD3 signaling axis. Furthermore, S1PR3 activity promotes the progression of human lung adenocarcinomas. Therefore, S1PR3 may represent a novel therapeutic target for the treatment of deadly lung adenocarcinomas.
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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.