ArticleMolecular cancer research : MCR2012
Cdc42 and the guanine nucleotide exchange factors Ect2 and trio mediate Fn14-induced migration and invasion of glioblastoma cells.
Article in Molecular cancer research : MCR, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
61 citing papers in PubMed, 1 synthesis or guideline pooled it, 90 citations in OpenAlex.
- Systematic review of protein biomarkers of invasive behavior in glioblastoma.Molecular neurobiology · 2014Pooled it
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- Bioinformatics Examination of Glioblastoma Identifies a Potential Panel of Therapeutic Biomarkers.Asian Pacific journal of cancer prevention : APJCP · 2024Article
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- SOXC Enhances NGN2-Mediated Reprogramming of Glioblastoma Cells Into Neuron-Like Cells by Modulating RhoA and RAC1/CDC42 Pathway Activity.CNS neuroscience & therapeutics · 2024Article
- Targeting small GTPases: emerging grasps on previously untamable targets, pioneered by KRAS.Signal transduction and targeted therapy · 2023Review
- Increased expression of ECT2 predicts the poor prognosis of breast cancer patients.Experimental hematology & oncology · 2022Article
- Role of the Hippo pathway in liver regeneration and repair: recent advances.Inflammation and regeneration · 2022Review
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- Targeting fibroblast growth factor (FGF)-inducible 14 (Fn14) for tumor therapy.Frontiers in pharmacology · 2022Review
- Novel CTRP8-RXFP1-JAK3-STAT3 axis promotes Cdc42-dependent actin remodeling for enhanced filopodia formation and motility in human glioblastoma cells.Molecular oncology · 2022Article
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- Epithelial cell transforming 2 is regulated by Yes-associated protein 1 and mediates pancreatic cancer progression and metastasis.American journal of physiology. Gastrointestinal and liver physiology · 2021Article
- A Novel Immune-Related Prognostic Biomarker and Target Associated With Malignant Progression of Glioma.Frontiers in oncology · 2021Article
- Local Delivery and Glioblastoma: Why Not Combining Sustained Release and Targeting?Frontiers in medical technology · 2021Review
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- The Role of Rho GTPases in Motility and Invasion of Glioblastoma Cells.Analytical cellular pathology (Amsterdam) · 2020Review
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- Hyperplasia suppressor gene inhibits the proliferation and metastasis of glioma cells by targeting rho family proteins.International journal of clinical and experimental pathology · 2020Article
1 more citing papers are in PubMed but not listed here.
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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 5 institutions in 1 country.
Funding
Abstract
Malignant glioblastomas are characterized by their ability to infiltrate into normal brain. We previously reported that binding of the multifunctional cytokine TNF-like weak inducer of apoptosis (TWEAK) to its receptor fibroblast growth factor-inducible 14 (Fn14) induces glioblastoma cell invasion via Rac1 activation. Here, we show that Cdc42 plays an essential role in Fn14-mediated activation of Rac1. TWEAK-treated glioma cells display an increased activation of Cdc42, and depletion of Cdc42 using siRNA abolishes TWEAK-induced Rac1 activation and abrogates glioma cell migration and invasion. In contrast, Rac1 depletion does not affect Cdc42 activation by Fn14, showing that Cdc42 mediates TWEAK-stimulated Rac1 activation. Furthermore, we identified two guanine nucleotide exchange factors (GEF), Ect2 and Trio, involved in TWEAK-induced activation of Cdc42 and Rac1, respectively. Depletion of Ect2 abrogates both TWEAK-induced Cdc42 and Rac1 activation, as well as subsequent TWEAK-Fn14-directed glioma cell migration and invasion. In contrast, Trio depletion inhibits TWEAK-induced Rac1 activation but not TWEAK-induced Cdc42 activation. Finally, inappropriate expression of Fn14 or Ect2 in mouse astrocytes in vivo using an RCAS vector system for glial-specific gene transfer in G-tva transgenic mice induces astrocyte migration within the brain, corroborating the in vitro importance of the TWEAK-Fn14 signaling cascade in glioblastoma invasion. Our results suggest that the TWEAK-Fn14 signaling axis stimulates glioma cell migration and invasion through two GEF-GTPase signaling units, Ect2-Cdc42 and Trio-Rac1. Components of the Fn14-Rho GEF-Rho GTPase signaling pathway present innovative drug targets for glioma therapy.
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