ArticleMolecular biology of the cell2001
Tumor necrosis factor-alpha induces stress fiber formation through ceramide production: role of sphingosine kinase.
Article in Molecular biology of the cell, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 65 citations in OpenAlex.
- Curcumin as a ceramide metabolism-targeting agent: Molecular mechanisms and therapeutic implications in cancer.Molecular biology reports · 2026Review
- TNF inhibits SARS-CoV-2 induced cell-cell fusion through activating the SDC4-RhoA signaling to promote actin bundles formation.Cell insight · 2026Article
- Lunar and Martian gravity alter immune cell interactions with endothelia in parabolic flight.NPJ microgravity · 2025Article
- Opaganib Downregulates N-Myc Expression and Suppresses In Vitro and In Vivo Growth of Neuroblastoma Cells.Cancers · 2024Article
- Signaling controversy and future therapeutical perspectives of targeting sphingolipid network in cancer immune editing and resistance to tumor necrosis factor-α immunotherapy.Cell communication and signaling : CCS · 2024Review
- Article
- Cytokine-Mediated Inflammation in the Oral Cavity and Its Effect on Lipid Nanocarriers.Nanomaterials (Basel, Switzerland) · 2021Article
- Cx43 and the Actin Cytoskeleton: Novel Roles and Implications for Cell-Cell Junction-Based Barrier Function Regulation.Biomolecules · 2020Review
- RACking up ceramide-induced islet β-cell dysfunction.Biochemical pharmacology · 2018Review
- Voluntary exposure to a toxin: the genetic influence on ethanol consumption.Mammalian genome : official journal of the International Mammalian Genome Society · 2018Article
- Targeting Sphingosine Kinases for the Treatment of Cancer.Advances in cancer research · 2018Review
- Ceramide activation of RhoA/Rho kinase impairs actin polymerization during aggregated LDL catabolism.Journal of lipid research · 2017Article
- Inflammation Drives Retraction, Stiffening, and Nodule Formation via Cytoskeletal Machinery in a Three-Dimensional Culture Model of Aortic Stenosis.The American journal of pathology · 2016Article
- Translocator Protein-Mediated Stabilization of Mitochondrial Architecture during Inflammation Stress in Colonic Cells.PloS one · 2016Article
- TNF and MAP kinase signalling pathways.Seminars in immunology · 2014Review
- Bioactive sphingolipid metabolites modulate ovarian cancer cell structural mechanics.Integrative biology : quantitative biosciences from nano to macro · 2013Article
- TNF-receptor-1 adaptor protein FAN mediates TNF-induced B16 melanoma motility and invasion.British journal of cancer · 2013Article
- Regulation of cytoskeleton organization by sphingosine in a mouse cell model of progressive ovarian cancer.Biomolecules · 2013Article
- Sphingolipid metabolites modulate dielectric characteristics of cells in a mouse ovarian cancer progression model.Integrative biology : quantitative biosciences from nano to macro · 2013Article
- Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine that activates several signaling cascades. We determined the extent to which ceramide is a second messenger for TNF-alpha-induced signaling leading to cytoskeletal rearrangement in Rat2 fibroblasts. TNF-alpha, sphingomyelinase, or C(2)-ceramide induced tyrosine phosphorylation of focal adhesion kinase (FAK) and paxillin, and stress fiber formation. Ly 294002, a phosphatidylinositol 3-kinase (PI 3-K) inhibitor, or expression of dominant/negative Ras (N17) completely blocked C(2)-ceramide- and sphingomyelinase-induced tyrosine phosphorylation of FAK and paxillin and severely decreased stress fiber formation. The TNF-alpha effects were only partially inhibited. Dimethylsphingosine, a sphingosine kinase (SK) inhibitor, blocked stress fiber formation by TNF-alpha and C(2)-ceramide. TNF-alpha, sphingomyelinase, and C(2)-ceramide translocated Cdc42, Rac, and RhoA to membranes, and stimulated p21-activated protein kinase downstream of Ras-GTP, PI 3-K, and SK. Transfection with inactive RhoA inhibited the TNF-alpha- and C(2)-ceramide-induced stress fiber formation. Our results demonstrate that stimulation by TNF-alpha, which increases sphingomyelinase activity and ceramide formation, activates sphingosine kinase, Rho family GTPases, focal adhesion kinase, and paxillin. This novel pathway of ceramide signaling can account for approximately 70% of TNF-alpha-induced stress fiber formation and cytoskeletal reorganization.
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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.