ArticleOncogene2009
Upregulation of PIP3-dependent Rac exchanger 1 (P-Rex1) promotes prostate cancer metastasis.
Article in Oncogene, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers.
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Who cites it
98 citing papers in PubMed, 141 citations in OpenAlex.
- Targeting protein geranylgeranylation slows tumor development in a murine model of prostate cancer metastasis.Cancer biology & therapy · 2017Trial
- Inhibition of PREX1 Reverses Enzalutamide Resistance in Castration-Resistant Prostate Cancer.The world journal of men's health · 2026Article
- Association of Body Composition with Tumor Proteomics and Survival in Patients with Clear Cell Renal Cell Carcinoma.Cancers · 2026Article
- The Rho guanine-nucleotide exchange factor P-Rex2 exhibits structural and regulatory features distinct from the related RhoGEF P-Rex1.The Journal of biological chemistry · 2026Article
- P-Rex2 exhibits unique structural features and regulatory mechanisms distinct from the closely related RhoGEF P-Rex1.bioRxiv : the preprint server for biology · 2026Article
- P-Rex1 limits the agonist-induced internalization of GPCRs independently of its Rac-GEF activity.Cell reports · 2025Article
- Understanding P-Rex regulation: structural breakthroughs and emerging perspectives.Biochemical Society transactions · 2024Review
- New Mechanisms Underlying Oncogenesis in Dbl Family Rho Guanine Nucleotide Exchange Factors.Molecular pharmacology · 2024Review
- Betaglycan sustains HGF/Met signaling in lung cancer and endothelial cells promoting cell migration and tumor growth.Heliyon · 2024Article
- Data mining-based identification of epigenetic signatures with discrimination potential of lung adenocarcinoma and squamous cell carcinoma.Molecular biology reports · 2024Article
- ∆Np63α inhibits Rac1 activation and cancer cell invasion through suppression of PREX1.Cell death discovery · 2024Article
- Migration, invasion, and metastasis are mediated byFrontiers in oncology · 2024Article
- Phosphoinositides in New Spaces.Cold Spring Harbor perspectives in biology · 2023Review
- A Mouse Systems Genetics Approach Reveals Common and Uncommon Genetic Modifiers of Hepatic Lysosomal Enzyme Activities and Glycosphingolipids.International journal of molecular sciences · 2023Article
- Kinetic Changes of Ptdins (3,4,5) P3 within Fast and Slow Turnover Rates of Focal Adhesion.Reports of biochemistry & molecular biology · 2022Article
- Identification of prostate cancer subtypes based on immune signature scores in bulk and single-cell transcriptomes.Medical oncology (Northwood, London, England) · 2022Article
- P-Rex1 Signaling Hub in Lower Grade Glioma Patients, Found byFrontiers in oncology · 2022Article
- Small-molecule inhibitors of P-Rex guanine-nucleotide exchange factors.Small GTPases · 2022Article
- Role of Rho guanine nucleotide exchange factors in non-small cell lung cancer.Bioengineered · 2021Article
- Article
38 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Excessive activation of G-protein-coupled receptor (GPCR) and receptor tyrosine kinase (RTK) pathways has been linked to prostate cancer metastasis. Rac activation by guanine nucleotide exchange factors (GEFs) plays an important role in directional cell migration, a critical step of tumor metastasis cascades. We found that the upregulation of P-Rex1, a Rac-selective GEF synergistically activated by Gbetagamma freed during GPCR signaling, and PIP3, generated during either RTK or GPCR signaling, strongly correlates with metastatic phenotypes in both prostate cancer cell lines and human prostate cancer specimens. Silencing endogenous P-Rex1 in metastatic prostate cancer PC-3 cells selectively inhibited Rac activity and reduced cell migration and invasion in response to ligands of both epidermal growth factor receptor and G-protein-coupled CXC chemokine receptor 4. Conversely, expression of recombinant P-Rex1, but not its 'GEF-dead' mutant, in non-metastatic prostate cancer cells, such as CWR22Rv1, increased cell migration and invasion through Rac-dependent lamellipodia formation. More importantly, using a mouse xenograft model, we showed that the expression of P-Rex1, but not its mutant, induced lymph node metastasis of CWR22Rv1 cells without an effect on primary tumor growth. Thus, by functioning as a coincidence detector of chemotactic signals from both GPCRs and RTKs, P-Rex1-dependent activation of Rac promotes prostate cancer metastasis.
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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.