ArticleInternational journal of molecular sciences2021
Extracellular Sphingosine-1-Phosphate Downstream of EGFR Increases Human Glioblastoma Cell Survival.
Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
10 citing papers in PubMed, 9 citations in OpenAlex.
- The physiological and pathological effects of sphingolipid metabolism and signaling in the central nervous system.Brain pathology (Zurich, Switzerland) · 2026Review
- Sphingolipid metabolism and hematologic disorders: current understanding and future directions.Frontiers in physiology · 2026Review
- The Involvement of Ceramide, Sphingosine-1-Phosphate and Ganglioside GM1 in Regulating Some Nervous System Functions.International journal of molecular sciences · 2025Review
- Sphingosine-1-Phosphate Metabolic Pathway in Cancer: Implications for Therapeutic Targets.International journal of molecular sciences · 2025Review
- Sphingosine 1-Phosphate Stimulates ER to Golgi Ceramide Traffic to Promote Survival in T98G Glioma Cells.International journal of molecular sciences · 2024Article
- The role of sphingolipid rheostat in the adult-type diffuse glioma pathogenesis.Frontiers in cell and developmental biology · 2024Review
- Ceramide Is Involved in Temozolomide Resistance in Human Glioblastoma U87MG Overexpressing EGFR.International journal of molecular sciences · 2023Article
- Lipid Alterations in Glioma: A Systematic Review.Metabolites · 2022Review
- Ceramide and Sphingosine-1-Phosphate in Neurodegenerative Disorders and Their Potential Involvement in Therapy.International journal of molecular sciences · 2022Review
- The Role of Sphingolipids Metabolism in Cancer Drug Resistance.Frontiers in oncology · 2021Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Sphingosine-1-phosphate (S1P) is a crucial mediator involved in the progression of different cancers, including glioblastoma multiforme (GBM), the most frequent and deadly human brain tumor, characterized by extensive invasiveness and rapid cell growth. Most of GBMs overexpress the epidermal growth factor receptor (EGFR), and we investigated the possible link between S1P and EGFR signaling pathways, focusing on its role in GBM survival, using the U87MG human cell line overexpressing EGFR (EGFR+). We previously demonstrated that EGFR+ cells have higher levels of extracellular S1P and increased sphingosine kinase-1 (SK1) activity than empty vector expressing cells. Notably, we demonstrated that EGFR+ cells are resistant to temozolomide (TMZ), the standard chemotherapeutic drug in GBM treatment, and the inhibition of SK1 or S1P receptors made EGFR+ cells sensitive to TMZ; moreover, exogenous S1P reverted this effect, thus involving extracellular S1P as a survival signal in TMZ resistance in GBM cells. In addition, both PI3K/AKT and MAPK inhibitors markedly reduced cell survival, suggesting that the enhanced resistance to TMZ of EGFR+ cells is dependent on the increased S1P secretion, downstream of the EGFR-ERK-SK1-S1P pathway. Altogether, our study provides evidence of a functional link between S1P and EGFR signaling pathways enhancing the survival properties of GBM cells.
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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.