ArticleThe Journal of biological chemistry2010
Aberrant overexpression of the Rgl2 Ral small GTPase-specific guanine nucleotide exchange factor promotes pancreatic cancer growth through Ral-dependent and Ral-independent mechanisms.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 66 citations in OpenAlex.
- Targeting KRAS mutations: orchestrating cancer evolution and therapeutic challenges.Signal transduction and targeted therapy · 2025Review
- Macromolecular crystallography for mammalian body temperature in support of molecular biophysics methods.Biophysical reviews · 2025Review
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- [RGL1 overexpression promotes metastasis of colorectal cancer by upregulating motile focal adhesion assemblyNan fang yi ke da xue xue bao = Journal of Southern Medical University · 2025Article
- Structural insights into the complex of oncogenic KRas4BLife science alliance · 2024Article
- Review
- Low expression of RalGAPs associates with the poorer overall survival of head and neck squamous cell carcinoma.Translational cancer research · 2021Article
- Ral GTPase-activating protein regulates the malignancy of pancreatic ductal adenocarcinoma.Cancer science · 2021Article
- Epigenetic Alterations in Pancreatic Cancer Metastasis.Biomolecules · 2021Review
- Drivers of Gene Expression Dysregulation in Pancreatic Cancer.Trends in cancer · 2021Review
- Ral GTPase is essential for actin dynamics and Golgi apparatus distribution in mouse oocyte maturation.Cell division · 2021Article
- RGL2 Drives the Metastatic Progression of Colorectal Cancer via Preventing the Protein Degradation of β-Catenin and KRAS.Cancers · 2021Article
- κB-Ras and Ral GTPases regulate acinar to ductal metaplasia during pancreatic adenocarcinoma development and pancreatitis.Nature communications · 2020Article
- NK Response Correlates with HIV Decrease in Pegylated IFN-α2a-Treated Antiretroviral Therapy-Suppressed Subjects.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- Localization of RalB signaling at endomembrane compartments and its modulation by autophagy.Scientific reports · 2019Article
- KRAS: The Critical Driver and Therapeutic Target for Pancreatic Cancer.Cold Spring Harbor perspectives in medicine · 2018Review
- Oncogenic N-Ras Stimulates SRF-Mediated Transactivation via H3 Acetylation at Lysine 9.BioMed research international · 2018Article
- RAL GTPases: Biology and Potential as Therapeutic Targets in Cancer.Pharmacological reviews · 2018Review
- Ral signaling pathway in health and cancer.Cancer medicine · 2017Review
- Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Our recent studies established essential and distinct roles for RalA and RalB small GTPase activation in K-Ras mutant pancreatic ductal adenocarcinoma (PDAC) cell line tumorigencity, invasion, and metastasis. However, the mechanism of Ral GTPase activation in PDAC has not been determined. There are four highly related mammalian RalGEFs (RalGDS, Rgl1, Rgl2, and Rgl3) that can serve as Ras effectors. Whether or not they share distinct or overlapping functions in K-Ras-mediated growth transformation has not been explored. We found that plasma membrane targeting to mimic persistent Ras activation enhanced the growth-transforming activities of RalGEFs. Unexpectedly, transforming activity did not correlate directly with total cell steady-state levels of Ral activation. Next, we observed elevated Rgl2 expression in PDAC tumor tissue and cell lines. Expression of dominant negative Ral, which blocks RalGEF function, as well as interfering RNA suppression of Rgl2, reduced PDAC cell line steady-state Ral activity, growth in soft agar, and Matrigel invasion. Surprisingly, the effect of Rgl2 on anchorage-independent growth could not be rescued by constitutively activated RalA, suggesting a novel Ral-independent function for Rgl2 in transformation. Finally, we determined that Rgl2 and RalB both localized to the leading edge, and this localization of RalB was dependent on endogenous Rgl2 expression. In summary, our observations support nonredundant roles for RalGEFs in Ras-mediated oncogenesis and a key role for Rgl2 in Ral activation and Ral-independent PDAC growth.
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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.