ArticleOncogene2019
A feed-forward loop between nuclear translocation of CXCR4 and HIF-1α promotes renal cell carcinoma metastasis.
Article in Oncogene, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 77 citations in OpenAlex.
- Value of Ferritin Heavy Chain (FTH1) Expression in Diagnosis and Prognosis of Renal Cell Carcinoma.Medical science monitor : international medical journal of experimental and clinical research · 2019Pooled it
- Immunoexpression of CXCL12 and CXCR4 in giant cell granulomas of the jaws and giant cell tumor of bone.Medicina oral, patologia oral y cirugia bucal · 2026Article
- Association of B7H3 with HIF-1α nuclear expression indicates poor prognosis and therapeutic potential in gastric cancer.Frontiers in oncology · 2026Article
- Potential role ofAsia Oceania journal of nuclear medicine & biology · 2026Article
- P-Rex1 limits the agonist-induced internalization of GPCRs independently of its Rac-GEF activity.Cell reports · 2025Article
- Intracellular and nuclear CXCR4 signaling promotes terminal erythroblast differentiation and enucleation.Science signaling · 2025Article
- Non-Cytotoxic Photodynamic Therapy with Talaporfin Sodium Reduces the Expression of CXCR4 and Enhances Chemotherapeutic Efficacy in Undifferentiated Gastric Cancer Cell Line HGC27.Acta histochemica et cytochemica · 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
- Nutrients Lowering Obesity-Linked Chemokines Blamable for Metastasis.International journal of molecular sciences · 2025Review
- Tumor-initiating and metastasis-initiating cells of clear-cell renal cell carcinoma.Journal of biomedical science · 2025Review
- Article
- TGFBI promotes proliferation and epithelial-mesenchymal transition in renal cell carcinoma through PI3K/AKT/mTOR/HIF-1α pathway.Cancer cell international · 2024Article
- Heyingwuzi formulation alleviates diabetic retinopathy by promoting mitophagyWorld journal of diabetes · 2024Article
- CXCR4 Expression as a Prognostic Biomarker in Soft Tissue Sarcomas.Diagnostics (Basel, Switzerland) · 2024Article
- C-X-C chemokine receptor type 4 promotes tubular cell senescence and renal fibrosis through β-catenin-inhibited fatty acid oxidation.Journal of cellular and molecular medicine · 2024Article
- Extracellular vesicles from subjects with COPD modulate cancer initiating cells phenotype through HIF-1α shuttling.Cell death & disease · 2023Article
- Novel cancer treatment paradigm targeting hypoxia-induced factor in conjunction with current therapies to overcome resistance.Journal of experimental & clinical cancer research : CR · 2023Review
- RNF8 enhances the sensitivity of PD-L1 inhibitor against melanoma through ubiquitination of galectin-3 in stroma.Cell death discovery · 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
- Targeting fatty acid synthase modulates sensitivity of hepatocellular carcinoma to sorafenib via ferroptosis.Journal of experimental & clinical cancer research : CR · 2023Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CXC chemokine receptor 4 (CXCR4) has been suggested to play a critical role in cancer metastasis. Some studies have described CXCR4 nuclear localization in metastatic lesions of renal cell carcinoma (RCC), which has been suggested to be correlated with cancer metastasis. However, the underlying mechanism and clinical significance of CXCR4 nuclear localization remains unknown. Here, we show that CXCR4 nuclear localization is more likely to occur in RCC tissues, especially in metastases, and is associated with poor prognosis. CXCR4 nuclear localization requires its nuclear localization sequence (NLS, residues 146-RPRK-149). After the mutation of NLS in CXCR4, CXCR4 nuclear localization in RCC cells is lost. Nuclear localization of CXCR4 promoted RCC tumorigenicity both in vitro and in vivo. Mechanistically, we found that CXCR4 and hypoxia-inducible factor-1α (HIF-1α) colocalized in RCC cells and interacted with each other. Moreover, CXCR4 nuclear localization promoted nuclear accumulation of HIF-1α, thereby promoting the expression of genes downstream of HIF-1α. Reciprocally, nuclear HIF-1α promoted CXCR4 transcription, thus forming a feed-forward loop. Subcellular CXCR4 and HIF-1α expression levels were independent adverse prognostic factors and could be combined with TNM stage to generate a predictive nomogram of the clinical outcome of patients with RCC. Therefore, our findings indicate that CXCR4 nuclear translocation plays a critical role in RCC metastasis and may serve as a prognostic biomarker and potential therapeutic target.
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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.