ArticleCancer research2018
Targeting the SphK1/S1P/S1PR1 Axis That Links Obesity, Chronic Inflammation, and Breast Cancer Metastasis.
Article in Cancer research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 147 papers, 1 of them a synthesis that pooled it.
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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
147 citing papers in PubMed, 1 synthesis or guideline pooled it, 218 citations in OpenAlex.
- Bibliometric and visual analysis of human microbiome-breast cancer interactions: current insights and future directions.Frontiers in microbiology · 2024Pooled it
- Recent Advances in the Treatment of Thyroid Pathologies with Selenium-Containing Compounds, Nanoparticles and Nanocomplexes Based on Selenium and Selenoproteins.Biological trace element research · 2026Review
- Comprehensive Quantification of Oligoasthenozoospermia Induced by Obesity, Reproductive Toxicants, and Their Combination in Rat Models.Andrology · 2026Article
- Label-free cell phenotypic profiling of sphingosine-1-phosphate receptor 1 and discovery of its agonist from natural products.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- MEOX1 Coordinates Autocrine-Paracrine Programs via SPHK1/S1P to Promote Lymph Node Metastasis in Ovarian Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Article
- Sphingosine-1-phosphate induces pulmonary artery smooth muscle cell proliferation, migration and pulmonary arterial remodeling by modulating sonic hedgehog signaling effector FoxM1.Chinese medical journal · 2026Article
- SPHK1 deficiency promotes intestinal homeostasis by ameliorating ER stress-induced gastrointestinal injury during murine graft-versus-host disease.Science China. Life sciences · 2026Article
- Novel lipid metabolism-related gene signature associated with clinical and immune features in lung adenocarcinoma patients experiencing lymph node metastasis.Translational lung cancer research · 2026Article
- Metabolic regulation of tumor-associated macrophage function and immunotherapy in cancer.Cancer biology & medicine · 2026Review
- Emerging complexities of phospholipid metabolism in adipose tissue.Molecules and cells · 2026Review
- Targeting Sphingosine-1-Phosphate Signaling Attenuates Doxorubicin-Aggravated Bone Loss in Obese Breast Cancer Mice.Smart medicine · 2026Article
- Adipocyte-driven STAT3-ANGPT2-PTGIS axis promotes cutaneous metastasis in breast cancer and represents a targetable pathway.NPJ precision oncology · 2026Article
- Pan-cancer signaling landscape linked to endothelial and immune Sphingosine-1-phosphate receptor 1 (S1PR1) expression.In silico pharmacology · 2026Article
- Targeting Sphingolipids in Breast Cancer: From Tumor Biology to Therapeutic Strategies.Oncology research · 2026Review
- Study on the CHJ01 antitumor activity and mechanism via targeting sphingosine kinase 1 in A549 cells.Pharmaceutical science advances · 2025Article
- Conserved sphingolipid metabolism under transcriptomic diversity: a prognostic and therapeutic target in triple-negative breast cancer.Journal of translational medicine · 2025Article
- Targeting SPHK1 in macrophages remodels the tumor microenvironment and enhances anti-PD-1 immunotherapy efficacy in colorectal cancer liver metastasis.Cancer communications (London, England) · 2025Article
- Article
- Identification and Validation of a Macrophage Phagocytosis-Related Gene Signature for Prognostic Prediction in Colorectal Cancer (CRC).Current issues in molecular biology · 2025Article
87 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
17 authors at 3 institutions in 2 countries.
Funding
Abstract
Although obesity with associated inflammation is now recognized as a risk factor for breast cancer and distant metastases, the functional basis for these connections remain poorly understood. Here, we show that in breast cancer patients and in animal breast cancer models, obesity is a sufficient cause for increased expression of the bioactive sphingolipid mediator sphingosine-1-phosphate (S1P), which mediates cancer pathogenesis. A high-fat diet was sufficient to upregulate expression of sphingosine kinase 1 (SphK1), the enzyme that produces S1P, along with its receptor S1PR1 in syngeneic and spontaneous breast tumors. Targeting the SphK1/S1P/S1PR1 axis with FTY720/fingolimod attenuated key proinflammatory cytokines, macrophage infiltration, and tumor progression induced by obesity. S1P produced in the lung premetastatic niche by tumor-induced SphK1 increased macrophage recruitment into the lung and induced IL6 and signaling pathways important for lung metastatic colonization. Conversely, FTY720 suppressed IL6, macrophage infiltration, and S1P-mediated signaling pathways in the lung induced by a high-fat diet, and it dramatically reduced formation of metastatic foci. In tumor-bearing mice, FTY720 similarly reduced obesity-related inflammation, S1P signaling, and pulmonary metastasis, thereby prolonging survival. Taken together, our results establish a critical role for circulating S1P produced by tumors and the SphK1/S1P/S1PR1 axis in obesity-related inflammation, formation of lung metastatic niches, and breast cancer metastasis, with potential implications for prevention and treatment.
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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.