ArticleMolecular cancer2016
ARHGEF15 overexpression worsens the prognosis in patients with pancreatic ductal adenocarcinoma through enhancing the motility and proliferative activity of the cancer cells.
Article in Molecular cancer, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 17 citations in OpenAlex.
- Functional characterization of podocyte-expressed THSD7A in experimental membranous nephropathy.JCI insight · 2026Article
- Pancreatic cancer: molecular pathogenesis and emerging therapeutic strategies.Signal transduction and targeted therapy · 2026Review
- Pan-cancer signaling landscape linked to endothelial and immune Sphingosine-1-phosphate receptor 1 (S1PR1) expression.In silico pharmacology · 2026Article
- Stromal ARHGEF15 Correlates With Inflammatory EMT and Stromal-Immune Crosstalk During Inflammatory Bowel Disease-To-Colorectal Cancer Progression.Bioinformatics and biology insights · 2026Article
- Decoding Rho GTPase signalling networks in directed cell migration.Frontiers in cell and developmental biology · 2026Review
- A nomogram integrating mutation signatures and clinical features for prognostic stratification in bladder cancer.Discover oncology · 2025Article
- Activity-dependent regulation of Cdc42 by Ephexin5 drives synapse growth and stabilization.Science advances · 2025Article
- Ephexin3/ARHGEF5 Together with Cell Migration Signaling Partners within the Tumor Microenvironment Define Prognostic Transcriptional Signatures in Multiple Cancer Types.International journal of molecular sciences · 2023Article
- Mutations in ARHGEF15 cause autosomal dominant hereditary cerebral small vessel disease and osteoporotic fracture.Acta neuropathologica · 2023Article
- FRL: An Integrative Feature Selection Algorithm Based on the Fisher Score, Recursive Feature Elimination, and Logistic Regression to Identify Potential Genomic Biomarkers.BioMed research international · 2021Article
- Patient-Derived Orthotopic Xenograft (PDOX) Mouse Models of Primary and Recurrent Meningioma.Cancers · 2020Article
- FARP1 boosts CDC42 activity from integrin αvβ5 signaling and correlates with poor prognosis of advanced gastric cancer.Oncogenesis · 2020Article
- High sulfite oxidase expression could predict postoperative biochemical recurrence in patients with prostate cancer.Medical molecular morphology · 2019Article
- Review
- A dual role for the RhoGEF Ephexin5 in regulation of dendritic spine outgrowth.Molecular and cellular neurosciences · 2017Article
- Sulfite Oxidase Is a Novel Prognostic Biomarker of Advanced Gastric Cancer.In vivo (Athens, Greece)Article
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive neoplastic diseases, associated with a remarkably poor prognosis. However, the molecular mechanisms underlying the development of PDAC remain elusive. The aim of this study was to identify genes whose expressions are correlated with a poor prognosis in PDAC patients, and to unravel the mechanisms underlying the involvement of these genes in the development of the cancer.
methodsGlobal gene expression profiling was conducted in 39 specimens obtained from Japanese patients with PDAC to identify genes whose expressions were correlated with a shorter overall survival. The effect of gene silencing or overexpression of ARHGEF15 in pancreatic cancer cell lines was examined by introducing siRNAs of ARHGEF15 or the ARHGEF15 expression vector. After assessing the effect of ARHGEF15 deregulation on the Rho-family proteins by pull-down assay, wound healing, transwell and cell viability assays were carried out to investigate the cellular phenotypes caused by the perturbation.
resultsThe global mRNA expression profiling revealed that overexpression of ARHGEF15, a Rho-specific GEF, was significantly associated with a poor prognosis in patients with PDAC. We also found that the depletion of ARHGEF15 by RNA interference in pancreatic cancer cell lines downregulated the activities of molecules of the Rho signaling pathway, including RhoA, Cdc42 and Rac1. Then, we also showed that ARHGEF15 silencing significantly reduced the motility and viability of the cells, while its overexpression resulted in the development of the opposite phenotype in multiple pancreatic cancer cell lines.
conclusionThese data suggest that upregulation of ARHGEF15 contributes to the development of aggressive PDAC by increasing the growth and motility of the pancreatic cancer cells, thereby worsening the prognosis of these patients. Therefore, ARHGEF15 could serve as a novel therapeutic target in patients with PDAC.
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