ArticleThe Journal of biological chemistry2014
The Ras-related protein, Rap1A, mediates thrombin-stimulated, integrin-dependent glioblastoma cell proliferation and tumor growth.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 54 citations in OpenAlex.
- ARHGAP20 organizes spatial Rap1-RhoA signaling coordination controlling adhesion dynamics during migration.bioRxiv : the preprint server for biology · 2026Article
- The GPCR Connection: Linking Alzheimer's Disease and Glioblastoma.Journal of cellular and molecular medicine · 2026Review
- The impact of compression and confinement in tumor growth and progression: emerging concepts in cancer mechanobiology.Frontiers in materials · 2025Article
- pH-sensing GPR68 inhibits vascular smooth muscle cell proliferation through Rap1A.American journal of physiology. Heart and circulatory physiology · 2024Article
- Hsp70 and Calcitonin Receptor Protein in Extracellular Vesicles from Glioblastoma Multiforme: Biomarkers with Putative Roles in Carcinogenesis and Potential for Differentiating Tumor Types.International journal of molecular sciences · 2024Article
- Rap1 in the Context of PCSK9, Atherosclerosis, and Diabetes.Current atherosclerosis reports · 2023Review
- EGFL7 expression profile in IDH-wildtype glioblastomas is associated with poor patient outcome.Journal of pathology and translational medicine · 2022Article
- Timosaponin AIII Suppresses RAP1 Signaling Pathway to Enhance the Inhibitory Effect of Paclitaxel on Nasopharyngeal Carcinoma.Computational and mathematical methods in medicine · 2022Article
- Tumor-associated macrophages (TAMs) depend on MMP1 for their cancer-promoting role.Cell death discovery · 2021Article
- C3G Protein, a New Player in Glioblastoma.International journal of molecular sciences · 2021Review
- Review
- Hypoxia Transcriptomic Modifications Induced by Proton Irradiation in U87 Glioblastoma Multiforme Cell Line.Journal of personalized medicine · 2021Article
- Phospholipase D1 is upregulated by vorinostat and confers resistance to vorinostat in glioblastoma.Journal of cellular physiology · 2021Article
- Elevated RGMA Expression Predicts Poor Prognosis in Patients with Glioblastoma.OncoTargets and therapy · 2021Article
- MAPK-RAP1A Signaling Enriched in Hepatocellular Carcinoma Is Associated With Favorable Tumor-Infiltrating Immune Cells and Clinical Prognosis.Frontiers in oncology · 2021Article
- A Signature of Nine lncRNA Methylated Genes Predicts Survival in Patients With Glioma.Frontiers in oncology · 2021Article
- Phospholipase D1 inhibition sensitizes glioblastoma to temozolomide and suppresses its tumorigenicity.The Journal of pathology · 2020Article
- Review
- Identification of miRNA signature associated with BMP2 and chemosensitivity of TMZ in glioblastoma stem-like cells.Genes & diseases · 2020Article
- Coagulation factor 2 thrombin receptor promotes malignancy in glioma under SOX2 regulation.Aging · 2020Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Rap1 is a Ras family GTPase with a well documented role in ERK/MAP kinase signaling and integrin activation. Stimulation of the G-protein-coupled receptor PAR-1 with thrombin in human 1321N1 glioblastoma cells led to a robust increase in Rap1 activation. This response was sustained for up to 6 h and mediated through RhoA and phospholipase D (PLD). Thrombin treatment also induced a 5-fold increase in cell adhesion to fibronectin, which was blocked by down-regulating PLD or Rap1A or by treatment with a β1 integrin neutralizing antibody. In addition, thrombin treatment led to increases in phospho-focal adhesion kinase (tyrosine 397), ERK1/2 phosphorylation and cell proliferation, which were significantly inhibited in cells treated with β1 integrin antibody or Rap1A siRNA. To assess the role of Rap1A in tumor formation in vivo, we compared growth of 1321N1 cells stably expressing control, Rap1A or Rap1B shRNA in a mouse xenograft model. Deletion of Rap1A, but not of Rap1B, reduced tumor mass by >70% relative to control. Similar observations were made with U373MG glioblastoma cells in which Rap1A was down-regulated. Collectively, these findings implicate a Rap1A/β1 integrin pathway, activated downstream of G-protein-coupled receptor stimulation and RhoA, in glioblastoma cell proliferation. Moreover, our data demonstrate a critical role for Rap1A in glioblastoma tumor growth in vivo.
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