ArticleJournal of lipid research2018
Sphingosine kinase 1 activation by estrogen receptor α36 contributes to tamoxifen resistance in breast cancer.
Article in Journal of lipid research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 37 citations in OpenAlex.
- The sphingolipid code of cancer: divergent roles across tumor types and therapeutic horizons.Molecular biology reports · 2026Review
- Nucleic sexual hormone receptor signaling pathways in breast cancer: function regulation, crosstalk, and therapeutic implications.NPJ precision oncology · 2026Review
- Targeting Sphingolipids in Breast Cancer: From Tumor Biology to Therapeutic Strategies.Oncology research · 2026Review
- Estrogen Receptors as Key Factors in Carcinogenesis.Biomedicines · 2025Review
- SPHK1 enhances olaparib resistance in ovarian cancer through the NFκB/NRF2/ferroptosis pathway.Cell death discovery · 2025Article
- Unraveling the Hippo pathway: YAP/TAZ as central players in cancer metastasis and drug resistance.EXCLI journal · 2025Review
- Review
- Interpetrosal sphingosine-1-phosphate ratio predicting Cushing's disease tumor laterality and remission after surgery.Frontiers in endocrinology · 2023Article
- Sphingosine kinase 1 mediates sexual dimorphism in fibrosis in a mouse model of NASH.Molecular metabolism · 2022Article
- Article
- The essential role of YAP in ERα36-mediated proliferation and the epithelial-mesenchymal transition in MCF-7 breast cancer cells.Frontiers in pharmacology · 2022Article
- Expression Profile of Sphingosine Kinase 1 Isoforms in Human Cancer Tissues and Cells: Importance and Clinical Relevance of the Neglected 1b-Isoform.Journal of oncology · 2022Article
- Article
- Plasma Sphingosine-1-Phosphate Levels Are Associated with Progression of Estrogen Receptor-Positive Breast Cancer.International journal of molecular sciences · 2021Article
- Review
- Sphingosine kinases negatively regulate the expression of matrix metalloproteases (Reproductive medicine and biology · 2021Article
- Potentiating Therapeutic Effects of Epidermal Growth Factor Receptor Inhibition in Triple-Negative Breast Cancer.Pharmaceuticals (Basel, Switzerland) · 2021Review
- 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
- Targeting defective sphingosine kinase 1 in Niemann-Pick type C disease with an activator mitigates cholesterol accumulation.The Journal of biological chemistry · 2020Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
In breast cancer, 17β-estradiol (E2) plays critical roles mainly by binding to its canonical receptor, estrogen receptor (ER) α66, and eliciting genomic effects. E2 also triggers rapid, nongenomic responses. E2 activates sphingosine kinase 1 (SphK1), increasing sphingosine-1-phosphate (S1P) that binds to its receptors, leading to important breast cancer signaling. However, the E2 receptor responsible for SphK1 activation has not yet been identified. Here, we demonstrate in triple-negative breast cancer cells, which lack the canonical ERα66 but express the novel splice variant ERα36, that ERα36 is the receptor responsible for E2-induced activation of SphK1 and formation and secretion of S1P and dihydro-S1P, the ligands for S1PRs. Tamoxifen, the first-line endocrine therapy for breast cancer, is an antagonist of ERα66, but an agonist of ERα36, and, like E2, activates SphK1 and markedly increases secretion of S1P. A major problem with tamoxifen therapy is development of acquired resistance. We found that tamoxifen resistance correlated with increased SphK1 and ERα36 expression in tamoxifen-resistant breast cancer cells, in patient-derived xenografts, and in endocrine-resistant breast cancer patients. Our data also indicate that targeting this ERα36 and SphK1 axis may be a therapeutic option to circumvent endocrine resistance and improve patient outcome.
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