ArticleThe Journal of biological chemistry2010
Sphingosine 1-phosphate receptor 4 uses HER2 (ERBB2) to regulate extracellular signal regulated kinase-1/2 in MDA-MB-453 breast cancer cells.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 80 citations in OpenAlex.
- Targeting Sphingolipids in Breast Cancer: From Tumor Biology to Therapeutic Strategies.Oncology research · 2026Review
- Article
- Targeting Sphingosine-1-Phosphate Signaling in Breast Cancer.International journal of molecular sciences · 2024Review
- The relationship between sphingosine-1-phosphate receptor 2 and epidermal growth factor in migration and invasion of oral squamous cell carcinoma.Cancer cell international · 2023Article
- The sphingosine 1-phosphate receptor 2/4 antagonist JTE-013 elicits off-target effects on sphingolipid metabolism.Scientific reports · 2022Article
- Inhibition of Sphingosine-1-Phosphate Receptor 2 by JTE013 Promoted Osteogenesis by Increasing Vesicle Trafficking, Wnt/CaInternational journal of molecular sciences · 2021Article
- Targeting the Sphingosine Kinase/Sphingosine-1-Phosphate Signaling Axis in Drug Discovery for Cancer Therapy.Cancers · 2021Review
- Sphingosine Kinase 1 Signaling in Breast Cancer: A Potential Target to Tackle Breast Cancer Stem Cells.Frontiers in molecular biosciences · 2021Review
- S1PScientific reports · 2019Article
- Curbing Lipids: Impacts ON Cancer and Viral Infection.International journal of molecular sciences · 2019Review
- Roles of sphingosine-1-phosphate signaling in cancer.Cancer cell international · 2019Review
- Article
- Genetic deletion of sphingosine kinase 1 suppresses mouse breast tumor development in an HER2 transgenic model.Carcinogenesis · 2018Article
- The Role of S1P and the Related Signaling Pathway in the Development of Tissue Fibrosis.Frontiers in pharmacology · 2018Review
- Does the Sphingosine 1-Phosphate Receptor-1 Provide a Better or Worse Prognostic Outcome for Breast Cancer Patients?Frontiers in oncology · 2018Article
- Pleiotropic effects of sphingosine-1-phosphate signaling to control human chorionic mesenchymal stem cell physiology.Cell death & disease · 2017Article
- Mammalian sphingosine kinase (SphK) isoenzymes and isoform expression: challenges for SphK as an oncotarget.Oncotarget · 2017Review
- Targeting sphingosine kinase 1 induces MCL1-dependent cell death in acute myeloid leukemia.Blood · 2017Article
- Beyond Immune Cell Migration: The Emerging Role of the Sphingosine-1-phosphate Receptor S1PR4 as a Modulator of Innate Immune Cell Activation.Mediators of inflammation · 2017Review
- Clinical Impact of Sphingosine-1-Phosphate in Breast Cancer.Mediators of inflammation · 2017Review
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
We demonstrate here that the bioactive lipid sphingosine 1-phosphate (S1P) uses sphingosine 1-phosphate receptor 4 (S1P(4)) and human epidermal growth factor receptor 2 (HER2) to stimulate the extracellular signal regulated protein kinase 1/2 (ERK-1/2) pathway in MDA-MB-453 cells. This was based on several lines of evidence. First, the S1P stimulation of ERK-1/2 was abolished by JTE013, which we show here is an S1P(2/4) antagonist and reduced by siRNA knockdown of S1P(4). Second, the S1P-stimulated activation of ERK-1/2 was almost completely abolished by a HER2 inhibitor (ErbB2 inhibitor II) and reduced by siRNA knockdown of HER2 expression. Third, phyto-S1P, which is an S1P(4) agonist, stimulated ERK-1/2 activation in an S1P(4)- and HER2-dependent manner. Fourth, FTY720 phosphate, which is an agonist at S1P(1,3,4,5) but not S1P(2) stimulated activation of ERK-1/2. Fifth, S1P stimulated the tyrosine phosphorylation of HER2, which was reduced by JTE013. HER2 which is an orphan receptor tyrosine kinase is the preferred dimerization partner of the EGF receptor. However, EGF-stimulated activation of ERK-1/2 was not affected by siRNA knockdown of HER2 or by ErbB2 (epidermal growth factor receptor 2 (or HER2)) inhibitor II in MDA-MB-453 cells. Moreover, S1P-stimulated activation of ERK-1/2 does not require an EGF receptor. Thus, S1P and EGF function in a mutually exclusive manner. In conclusion, the magnitude of the signaling gain on the ERK-1/2 pathway produced in response to S1P can be increased by HER2 in MDA-MB-453 cells. The linkage of S1P with an oncogene suggests that S1P and specifically S1P(4) may have an important role in breast cancer progression.
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