ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2008
EGF regulates plasminogen activator inhibitor-1 (PAI-1) by a pathway involving c-Src, PKCdelta, and sphingosine kinase 1 in glioblastoma cells.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
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Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 87 citations in OpenAlex.
- Sphingosine 1-phosphate (S1P) signaling in glioblastoma multiforme-A systematic review.International journal of molecular sciences · 2017Pooled it
- The physiological and pathological effects of sphingolipid metabolism and signaling in the central nervous system.Brain pathology (Zurich, Switzerland) · 2026Review
- Article
- Sphingosine-1-phosphate signaling regulates the ability of Müller glia to become neurogenic, proliferating progenitor-like cells.bioRxiv : the preprint server for biology · 2025Article
- Review
- Cancer-Associated Fibroblasts: Mechanisms of Tumor Progression and Novel Therapeutic Targets.Cancers · 2022Review
- Upregulation of Atypical Cadherin FAT1 Promotes an Immunosuppressive Tumor MicroenvironmentFrontiers in immunology · 2022Article
- Differential Expression of the Sphingolipid Pathway Is Associated with Sensitivity to the PP2A Activator FTY720 in Colorectal Cancer Cell Lines.Journal of clinical medicine · 2021Article
- Adipocyte-Derived Leptin Promotes PAI-1 -Mediated Breast Cancer Metastasis in a STAT3/miR-34a Dependent Manner.Cancers · 2020Article
- Sphingosine-1-Phosphate in the Tumor Microenvironment: A Signaling Hub Regulating Cancer Hallmarks.Cells · 2020Review
- Palbociclib Effectively Halts Proliferation but Fails to Induce Senescence in Patient-Derived Glioma Stem Cells.Molecular neurobiology · 2019Article
- Dysfunctional ErbB2, an EGF receptor family member, hinders repair of airway epithelial cells from asthmatic patients.The Journal of allergy and clinical immunology · 2019Article
- The Role of Fibrinolytic Regulators in Vascular Dysfunction of Systemic Sclerosis.International journal of molecular sciences · 2019Review
- An intrinsic lipid-binding interface controls sphingosine kinase 1 function.Journal of lipid research · 2018Article
- Expansion of Sphingosine Kinase and Sphingosine-1-Phosphate Receptor Function in Normal and Cancer Cells: From Membrane Restructuring to Mediation of Estrogen Signaling and Stem Cell Programming.International journal of molecular sciences · 2018Review
- Review
- Negative control of the HGF/c-MET pathway by TGF-β: a new look at the regulation of stemness in glioblastoma.Cell death & disease · 2017Article
- Co-dependency of PKCδ and K-Ras: inverse association with cytotoxic drug sensitivity in KRAS mutant lung cancer.Oncogene · 2017Article
- EGFR and EGFRvIII Promote Angiogenesis and Cell Invasion in Glioblastoma: Combination Therapies for an Effective Treatment.International journal of molecular sciences · 2017Review
- Multifunctional roles of PKCδ: Opportunities for targeted therapy in human disease.Pharmacology & therapeutics · 2016Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Patients with gliomas expressing high levels of epidermal growth factor receptor (EGFR) and plasminogen activator inhibitor-1 (PAI-1) have a shorter overall survival prognosis. Moreover, EGF enhances PAI-1 expression in glioma cells. Although multiple known signaling cascades are activated by EGF in glioma cells, we show for the first time that EGF enhances expression of PAI-1 via sequential activation of c-Src, protein kinase C delta (PKCdelta), and sphingosine kinase 1 (SphK1), the enzyme that produces sphingosine-1-phosphate. EGF induced rapid phosphorylation of c-Src and PKCdelta and concomitant translocation of PKCdelta as well as SphK1 to the plasma membrane. Down-regulation of PKCdelta abolished EGF-induced SphK1 translocation and up-regulation of PAI-1 by EGF; whereas, down-regulation of PKCalpha had no effect on the EGF-induced PAI-1 activation but enhanced its basal expression. Similarly, inhibition of c-Src activity by PP2 blocked both EGF-induced translocation of SphK1 and PKCdelta to the plasma membrane and up-regulation of PAI-1 expression. Furthermore, SphK1 was indispensable for both EGF-induced c-Jun phosphorylation and PAI-1 expression. Collectively, our results provide a functional link between three critical downstream targets of EGF, c-Src, PKCdelta, and SphK1 that have all been implicated in regulating motility and invasion of glioma cells.
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Registered trials
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