ArticleProceedings of the National Academy of Sciences of the United States of America2016
Truncating PREX2 mutations activate its GEF activity and alter gene expression regulation in NRAS-mutant melanoma.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 56 citations in OpenAlex.
- Genetic analysis of primary lung interdigitating dendritic cell sarcomas.The Journal of pathology · 2026Article
- Variations in DNA Methylation Are Landmarks of Freshwater Adaptation in Three-Spined Sticklebacks.International journal of molecular sciences · 2026Article
- P-Rex2 suppresses glucose uptake into liver and skeletal muscle through different adaptor functions.Scientific reports · 2025Article
- Proteomics in pancreatic cancer.Biomarker research · 2025Review
- Targeting the PREX2/RAC1/PI3Kβ Signaling Axis Confers Sensitivity to Clinically Relevant Therapeutic Approaches in Melanoma.Cancer research · 2025Article
- AHCYL1 mediates the tumor-promoting effect of PREX2 in non-small cell lung carcinoma.Theranostics · 2025Article
- Pharmacological targeting of casein kinase 1δ suppresses oncogenic NRAS-driven melanoma.Nature communications · 2024Article
- Understanding P-Rex regulation: structural breakthroughs and emerging perspectives.Biochemical Society transactions · 2024Review
- Tumorigenesis driven by the BRAFbioRxiv : the preprint server for biology · 2024Article
- PREX2 contributes to radiation resistance by inhibiting radiotherapy-induced tumor immunogenicity via cGAS/STING/IFNs pathway in colorectal cancer.BMC medicine · 2024Article
- PAK1 and Therapy Resistance in Melanoma.Cells · 2023Review
- Small-molecule inhibitors of P-Rex guanine-nucleotide exchange factors.Small GTPases · 2022Article
- Article
- Non-BRAF Mutant Melanoma: Molecular Features and Therapeutical Implications.Frontiers in molecular biosciences · 2020Review
- Targeting Rac and Cdc42 GEFs in Metastatic Cancer.Frontiers in cell and developmental biology · 2020Review
- Rac-GEF/Rac Signaling and Metastatic Dissemination in Lung Cancer.Frontiers in cell and developmental biology · 2020Article
- RAC1Cancer cell · 2019Article
- Long Non-coding RNA LINC-PINT Suppresses Cell Proliferation and Migration of Melanoma via Recruiting EZH2.Frontiers in cell and developmental biology · 2019Article
- Review
- Molecular Pathways in Melanomagenesis: What We Learned from Next-Generation Sequencing Approaches.Current oncology reports · 2018Review
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Authors and funding
15 authors at 5 institutions in 4 countries.
Funding
Abstract
PREX2 (phosphatidylinositol-3,4,5-triphosphate-dependent Rac-exchange factor 2) is a PTEN (phosphatase and tensin homolog deleted on chromosome 10) binding protein that is significantly mutated in cutaneous melanoma and pancreatic ductal adenocarcinoma. Here, genetic and biochemical analyses were conducted to elucidate the nature and mechanistic basis of PREX2 mutation in melanoma development. By generating an inducible transgenic mouse model we showed an oncogenic role for a truncating PREX2 mutation (PREX2(E824)*) in vivo in the context of mutant NRAS. Using integrative cross-species gene expression analysis, we identified deregulated cell cycle and cytoskeleton organization as significantly perturbed biological pathways in PREX2 mutant tumors. Mechanistically, truncation of PREX2 activated its Rac1 guanine nucleotide exchange factor activity, abolished binding to PTEN and activated the PI3K (phosphatidyl inositol 3 kinase)/Akt signaling pathway. We further showed that PREX2 truncating mutations or PTEN deletion induces down-regulation of the tumor suppressor and cell cycle regulator CDKN1C (also known as p57(KIP2)). This down-regulation occurs, at least partially, through DNA hypomethylation of a differentially methylated region in chromosome 11 that is a known regulatory region for expression of the CDKN1C gene. Together, these findings identify PREX2 as a mediator of NRAS-mutant melanoma development that acts through the PI3K/PTEN/Akt pathway to regulate gene expression of a cell cycle regulator.
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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.