ArticleOncogene2013
Downregulation of Ral GTPase-activating protein promotes tumor invasion and metastasis of bladder cancer.
Article in Oncogene, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 58 citations in OpenAlex.
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- MetaCancerDB: a database of site-specific RNA-miRNA correlations in cancer metastasis.Database : the journal of biological databases and curation · 2026Article
- Integrative analysis of RAS signaling effectors reveals stage-dependent oncogenic patterns in colon adenocarcinoma.Biotechnology reports (Amsterdam, Netherlands) · 2025Article
- Structure and mechanism of the RalGAP tumor suppressor complex.Nature communications · 2025Article
- Regulation of Ras p21 and RalA GTPases activity by quinine in mammary epithelial cells.Molecular and cellular biochemistry · 2024Article
- Exploring Covalent Bond Formation at Tyr-82 for Inhibition of Ral GTPase Activation.ChemMedChem · 2023Article
- Antitumor Effects of Ral-GTPases Downregulation in Glioblastoma.International journal of molecular sciences · 2022Article
- Dysregulation of RalA signaling through dual regulatory mechanisms exerts its oncogenic functions in hepatocellular carcinoma.Hepatology (Baltimore, Md.) · 2022Article
- Review
- Covalent Fragment Screening Identifies Rgl2 RalGEF Cysteine for Targeted Covalent Inhibition of Ral GTPase Activation.ChemMedChem · 2022Article
- Article
- Low expression of RalGAPs associates with the poorer overall survival of head and neck squamous cell carcinoma.Translational cancer research · 2021Article
- Parallel Rap1>RalGEF>Ral and Ras signals sculpt the C. elegans nervous system.Developmental biology · 2021Article
- Ral GTPase-activating protein regulates the malignancy of pancreatic ductal adenocarcinoma.Cancer science · 2021Article
- The interaction between MALAT1 target, miR-143-3p, and RALGAPA2 is affected by functional SNP rs3827693 in breast cancer.Human cell · 2020Article
- κB-Ras and Ral GTPases regulate acinar to ductal metaplasia during pancreatic adenocarcinoma development and pancreatitis.Nature communications · 2020Article
- Identification of single-nucleotide variants associated with susceptibility to Salmonella in pigs using a genome-wide association approach.BMC veterinary research · 2020Article
- Faithful preclinical mouse models for better translation to bedside in the field of immuno-oncology.International journal of clinical oncology · 2020Review
- Small-molecule covalent bond formation at tyrosine creates a binding site and inhibits activation of Ral GTPases.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- The Rheb-TORC1 signaling axis functions as a developmental checkpoint.Development (Cambridge, England) · 2020Article
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Authors and funding
20 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The small GTPase Ral is known to be highly activated in several human cancers, such as bladder, colon and pancreas cancers. It is reported that activated Ral is involved in cell proliferation, migration and metastasis of bladder cancer. This protein is activated by Ral guanine nucleotide exchange factors (RalGEFs) and inactivated by Ral GTPase-activating proteins (RalGAPs), the latter of which consist of heterodimers containing a catalytic α1 or α2 subunit and a common β subunit. In Ras-driven cancers, such as pancreas and colon cancers, constitutively active Ras mutant activates Ral through interaction with RalGEFs, which contain the Ras association domain. However, little is known with regard to the mechanism that governs aberrant activation of Ral in bladder cancer, in which Ras mutations are relatively infrequent. Here, we show that Ral was highly activated in invasive bladder cancer cells due to reduced expression of RalGAPα2, the dominant catalytic subunit in bladder, rather than increased expression of RalGEFs. Exogenous expression of wild-type RalGAPα2 in KU7 bladder cancer cells with invasive phenotype, but not mutant RalGAPα2-N1742K lacking RalGAP activity, resulted in attenuated cell migration in vitro and lung metastasis in vivo. Furthermore, genetic ablation of Ralgapa2 promoted tumor invasion in a chemically-induced murine bladder cancer model. Importantly, immunohistochemical analysis of human bladder cancer specimens revealed that lower expression of RalGAPα2 was associated with advanced clinical stage and poor survival of patients. Collectively, these results are highly indicative that attenuated expression of RalGAPα2 leads to disease progression of bladder cancer through enhancement of Ral activity.
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