ArticlePloS one2013
Cysteine (C)-x-C receptor 4 undergoes transportin 1-dependent nuclear localization and remains functional at the nucleus of metastatic prostate cancer cells.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 67 citations in OpenAlex.
- The association of CXCR4 expression with clinicopathological significance and potential drug target in prostate cancer: a meta-analysis and literature review.Drug design, development and therapy · 2015Pooled it
- CXCR4, CXCL12 and the relative CXCL12-CXCR4 expression as prognostic factors in colon cancer.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Trial
- Nanocarrier-Based Systems for Targeted Delivery: Current Challenges and Future Directions.MedComm · 2025Review
- Intracellular and nuclear CXCR4 signaling promotes terminal erythroblast differentiation and enucleation.Science signaling · 2025Article
- Immunoexpression of CXCL12 and CXCR4 in oral tongue squamous cell carcinoma of young and older patients.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2025Article
- The Use of Biologics for Targeting GPCRs in Metastatic Cancers.Biotech (Basel (Switzerland)) · 2025Review
- CXCR4 Expression as a Prognostic Biomarker in Soft Tissue Sarcomas.Diagnostics (Basel, Switzerland) · 2024Article
- Acetate-Mediated Odorant Receptor OR51E2 Activation Results in Calcitonin Secretion in Parafollicular C-Cells: A Novel Diagnostic Target of Human Medullary Thyroid Cancer.Biomedicines · 2023Article
- Differential Expression and Clinical Relevance of C-X-C Motif Chemokine Receptor 4 (CXCR4) in Renal Cell Carcinomas, Benign Renal Tumors, and Metastases.International journal of molecular sciences · 2023Article
- Emerging RNA-Based Therapeutic and Diagnostic Options: Recent Advances and Future Challenges in Genitourinary Cancers.International journal of molecular sciences · 2023Review
- GPCRs in Intracellular Compartments: New Targets for Drug Discovery.Biomolecules · 2022Review
- Article
- Regulating Phase Transition in Neurodegenerative Diseases by Nuclear Import Receptors.Biology · 2022Review
- Molecular Landscape of LncRNAs in Prostate Cancer: A focus on pathways and therapeutic targets for intervention.Journal of experimental & clinical cancer research : CR · 2022Review
- Shuttling of cellular proteins between the plasma membrane and nucleus (Review).Molecular medicine reports · 2022Review
- CXCL12 May Drive Inflammatory Potential in the Ovine Corpus Luteum During Implantation.Reproductive sciences (Thousand Oaks, Calif.) · 2022Article
- Insights into Nuclear G-Protein-Coupled Receptors as Therapeutic Targets in Non-Communicable Diseases.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Review
- Serum deprivation initiates adaptation and survival to oxidative stress in prostate cancer cells.Scientific reports · 2020Article
- New insights into mechanisms of nuclear translocation of G-protein coupled receptors.Small GTPases · 2019Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
Abstract
The G-protein coupled receptor (GPCR), Cysteine (C)-X-C Receptor 4 (CXCR4), plays an important role in prostate cancer metastasis. CXCR4 is generally regarded as a plasma membrane receptor where it transmits signals that support transformation, progression and eventual metastasis. Due to the central role of CXCR4 in tumorigenesis, therapeutics approaches such as antagonist and monoclonal antibodies have focused on receptors that exist on the plasma membrane. An emerging concept for G-protein coupled receptors is that they may localize to and associate with the nucleus where they retain function and mediate nuclear signaling. Herein, we demonstrate that CXCR4 associated with the nucleus of malignant prostate cancer tissues. Likewise, expression of CXCR4 was detected in nuclear fractions among several prostate cancer cell lines, compared to normal prostate epithelial cells. Our studies identified a nuclear pool of CXCR4 and we defined a nuclear transport pathway for CXCR4. We reveal a putative nuclear localization sequence (NLS), 'RPRK', within CXCR4 that contributed to nuclear localization. Additionally, nuclear CXCR4 interacted with Transportinβ1 and Transportinβ1-binding to CXCR4 promoted its nuclear translocation. Importantly, Gαi immunoprecipitation and calcium mobilization studies indicated that nuclear CXCR4 was functional and participated in G-protein signaling, revealing that the nuclear pool of CXCR4 retained function. Given the suggestion that functional, nuclear CXCR4 may be a mechanism underlying prostate cancer recurrence, increased metastatic ability and poorer prognosis after tumors have been treated with therapy that targets plasma membrane CXCR4, these studies addresses a novel mechanism of nuclear signaling for CXCR4, a novel mechanism of clinical targeting, and demonstrate an active nuclear pool that provides important new information to illuminate what has been primarily clinical reports of nuclear CXCR4.
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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.