ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2015
Intracellular sphingosine kinase 2-derived sphingosine-1-phosphate mediates epidermal growth factor-induced ezrin-radixin-moesin phosphorylation and cancer cell invasion.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 62 citations in OpenAlex.
- Non-invasive detection of metastatic papillary thyroid carcinoma after radical surgery using salivary metabolomic biomarkers.Archives of endocrinology and metabolism · 2026Article
- Engineered Lipidic Nanomaterials Inspired by Sphingomyelin Metabolism for Cancer Therapy.Molecules (Basel, Switzerland) · 2023Review
- 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
- Targeting SPHK1/PBX1 Axis Induced Cell Cycle Arrest in Non-Small Cell Lung Cancer.International journal of molecular sciences · 2022Article
- Review
- Sphingolipids and Lymphomas: A Double-Edged Sword.Cancers · 2022Review
- Sphingosine-1-phosphate transporter spinster homolog 2 is essential for iron-regulated metastasis of hepatocellular carcinoma.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Keep a Little Fire Burning-The Delicate Balance of Targeting Sphingosine-1-Phosphate in Cancer Immunity.International journal of molecular sciences · 2022Review
- A Comprehensive Review: Sphingolipid Metabolism and Implications of Disruption in Sphingolipid Homeostasis.International journal of molecular sciences · 2021Review
- Bioactive sphingolipids: Advancements and contributions from the laboratory of Dr. Lina M. Obeid.Cellular signalling · 2021Review
- SPNS2 Downregulation Induces EMT and Promotes Colorectal Cancer MetastasisFrontiers in oncology · 2021Article
- Elusive Roles of the Different Ceramidases in Human Health, Pathophysiology, and Tissue Regeneration.Cells · 2020Review
- Sphingosine 1-Phosphate Signaling and Metabolism in Chemoprevention and Chemoresistance in Colon Cancer.Molecules (Basel, Switzerland) · 2020Review
- Sphingosine 1-Phosphate (S1P)/ S1P Receptor Signaling and Mechanotransduction: Implications for Intrinsic Tissue Repair/Regeneration.International journal of molecular sciences · 2019Review
- The endothelial tip-stalk cell selection and shuffling during angiogenesis.Journal of cell communication and signaling · 2019Review
- Sphingolipid-Transporting Proteins as Cancer Therapeutic Targets.International journal of molecular sciences · 2019Review
- New insights into functions of the sphingosine-1-phosphate transporter SPNS2.Journal of lipid research · 2019Review
- Sphingosine kinase 2 promotes lipotoxicity in pancreatic β-cells and the progression of diabetes.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- S1P/S1PR3 axis promotes aerobic glycolysis by YAP/c-MYC/PGAM1 axis in osteosarcoma.EBioMedicine · 2019Article
- Thrombin Contributes to Anti-myeloperoxidase Antibody Positive IgG-Mediated Glomerular Endothelial Cells Activation Through SphK1-S1P-S1PR3 Signaling.Frontiers in immunology · 2019Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
The bioactive sphingolipid sphingosine-1-phosphate (S1P) mediates cellular proliferation, mitogenesis, inflammation, and angiogenesis. These biologies are mediated through S1P binding to specific GPCRs [sphingosine-1-phosphate receptor (S1PR)1-5] and some other less well-characterized intracellular targets. Ezrin-radixin-moesin (ERM) proteins, a family of adaptor molecules linking the cortical actin cytoskeleton to the plasma membrane, are emerging as critical regulators of cancer invasion via regulation of cell morphology and motility. Recently, we identified S1P as an acute ERM activator (via phosphorylation) through its action on S1PR2. In this work, we dissect the mechanism of S1P generation downstream of epidermal growth factor (EGF) leading to ERM phosphorylation and cancer invasion. Using pharmacologic inhibitors, small interfering RNA technologies, and genetic approaches, we demonstrate that sphingosine kinase (SK)2, and not SK1, is essential and sufficient in EGF-mediated ERM phosphorylation in HeLa cells. In fact, knocking down SK2 decreased ERM activation 2.5-fold. Furthermore, we provide evidence that SK2 is necessary to mediate EGF-induced invasion. In addition, overexpressing SK2 causes a 2-fold increase in HeLa cell invasion. Surprisingly, and for the first time, we find that this event, although dependent on S1PR2 activation, does not generate and does not require extracellular S1P secretion, therefore introducing a potential novel model of autocrine/intracrine action of S1P that still involves its GPCRs. These results define new mechanistic insights for EGF-mediated invasion and novel actions of SK2, therefore setting the stage for novel targets in the treatment of growth factor-driven malignancies.
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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.