ArticleThe Journal of biological chemistry2013
The Src homology 3 domain-containing guanine nucleotide exchange factor is overexpressed in high-grade gliomas and promotes tumor necrosis factor-like weak inducer of apoptosis-fibroblast growth factor-inducible 14-induced cell migration and invasion via tumor necrosis factor receptor-associated factor 2.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 31 citations in OpenAlex.
- Review
- Review
- Anti-Fn14-Conjugated Prussian Blue Nanoparticles as a Targeted Photothermal Therapy Agent for Glioblastoma.Nanomaterials (Basel, Switzerland) · 2022Article
- Targeting fibroblast growth factor (FGF)-inducible 14 (Fn14) for tumor therapy.Frontiers in pharmacology · 2022Review
- Targeting the Ubiquitin System in Glioblastoma.Frontiers in oncology · 2020Review
- The Role of Rho GTPases in Motility and Invasion of Glioblastoma Cells.Analytical cellular pathology (Amsterdam) · 2020Review
- PDZ-RhoGEF Is a Signaling Effector for TROY-Induced Glioblastoma Cell Invasion and Survival.Neoplasia (New York, N.Y.) · 2018Article
- Genetic Alterations of TRAF Proteins in Human Cancers.Frontiers in immunology · 2018Review
- Prognostic Significance of TNFR-Associated Factor 1 and 2 (TRAF1 and TRAF2) in Glioblastoma.Medical science monitor : international medical journal of experimental and clinical research · 2017Article
- A RhoG-mediated signaling pathway that modulates invadopodia dynamics in breast cancer cells.Journal of cell science · 2017Article
- Identification of aurintricarboxylic acid as a selective inhibitor of the TWEAK-Fn14 signaling pathway in glioblastoma cells.Oncotarget · 2017Article
- TWEAK/Fn14 Activation Participates in Skin Inflammation.Mediators of inflammation · 2017Review
- TWEAK activation of the non-canonical NF-κB signaling pathway differentially regulates melanoma and prostate cancer cell invasion.Oncotarget · 2016Article
- The TWEAK receptor Fn14 is a potential cell surface portal for targeted delivery of glioblastoma therapeutics.Oncogene · 2016Review
- SGEF Is Regulated via TWEAK/Fn14/NF-κB Signaling and Promotes Survival by Modulation of the DNA Repair Response to Temozolomide.Molecular cancer research : MCR · 2016Article
- Propentofylline inhibits glioblastoma cell invasion and survival by targeting the TROY signaling pathway.Journal of neuro-oncology · 2016Article
- Repair Injured Heart by Regulating Cardiac Regenerative Signals.Stem cells international · 2016Review
- Article
- FN14 expression correlates with MET in NSCLC and promotes MET-driven cell invasion.Clinical & experimental metastasis · 2014Article
- Mcl-1 mediates TWEAK/Fn14-induced non-small cell lung cancer survival and therapeutic response.Molecular cancer research : MCR · 2014Article
Corrections and comments
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Authors and funding
6 authors at 5 institutions in 1 country.
Funding
Abstract
Glioblastoma (GB) is the highest grade of primary adult brain tumors, characterized by a poorly defined and highly invasive cell population. Importantly, these invading cells are attributed with having a decreased sensitivity to radiation and chemotherapy. TNF-like weak inducer of apoptosis (TWEAK)-Fn14 ligand-receptor signaling is one mechanism in GB that promotes cell invasiveness and survival and is dependent upon the activity of multiple Rho GTPases, including Rac1. Here we report that Src homology 3 domain-containing guanine nucleotide exchange factor (SGEF), a RhoG-specific guanine nucleotide exchange factor, is overexpressed in GB tumors and promotes TWEAK-Fn14-mediated glioma invasion. Importantly, levels of SGEF expression in GB tumors inversely correlate with patient survival. SGEF mRNA expression is increased in GB cells at the invasive rim relative to those in the tumor core, and knockdown of SGEF expression by shRNA decreases glioma cell migration in vitro and invasion ex vivo. Furthermore, we showed that, upon TWEAK stimulation, SGEF is recruited to the Fn14 cytoplasmic tail via TRAF2. Mutation of the Fn14-TRAF domain site or depletion of TNF receptor-associated factor 2 (TRAF2) expression by siRNA oligonucleotides blocked SGEF recruitment to Fn14 and inhibited SGEF activity and subsequent GB cell migration. We also showed that knockdown of either SGEF or RhoG diminished TWEAK activation of Rac1 and subsequent lamellipodia formation. Together, these results indicate that SGEF-RhoG is an important downstream regulator of TWEAK-Fn14-driven GB cell migration and invasion.
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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.