ArticleCell death & disease2014
CXCR4 and CXCR7 transduce through mTOR in human renal cancer cells.
Article in Cell death & disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 80 citations in OpenAlex.
- CXCR4, CXCR7 and PBRM1 are responsible for everolimus and cabozantinib resistance in human renal cancer cells.Cell death discovery · 2026Article
- CXCR4 Expression as a Prognostic Biomarker in Soft Tissue Sarcomas.Diagnostics (Basel, Switzerland) · 2024Article
- Crosstalk between CXCR4/ACKR3 and EGFR Signaling in Breast Cancer Cells.International journal of molecular sciences · 2022Article
- ABAT gene expression associated with the sensitivity of hypomethylating agents in myelodysplastic syndrome through CXCR4/mTOR signaling.Cell death discovery · 2022Article
- CXCR4/ACKR3/CXCL12 axis in the lymphatic metastasis of vulvar squamous cell carcinoma.Journal of clinical pathology · 2022Article
- MicroRNA-200b-3p restrains gastric cancer cell proliferation, migration, and invasion via C-X-C motif chemokine ligand 12/CXC chemokine receptor 7 axis.Bioengineered · 2022Article
- The functions and prognostic values of chemokine and chemokine receptors in gastric cancer.American journal of cancer research · 2022Article
- Qingluoyin granules protect against adjuvant-induced arthritis in rats via downregulating the CXCL12/CXCR4-NF-κB signalling pathway.Pharmaceutical biology · 2021Article
- Effects of SDF-1/CXCR7 on the Migration, Invasion and Epithelial-Mesenchymal Transition of Gastric Cancer Cells.Frontiers in genetics · 2021Article
- CXCL12 Signaling in the Tumor Microenvironment.Advances in experimental medicine and biology · 2021Review
- Pleiotropic Roles of CXCR4 in Wound Repair and Regeneration.Frontiers in immunology · 2021Review
- CXCR4 and CXCR7 Signaling Pathways: A Focus on the Cross-Talk Between Cancer Cells and Tumor Microenvironment.Frontiers in oncology · 2021Review
- Impact of inflammation and immunotherapy in renal cell carcinoma.Oncology letters · 2020Review
- Discovery of Diphenylacetamides as CXCR7 Inhibitors with Novel β-Arrestin Antagonist Activity.ACS medicinal chemistry letters · 2020Article
- New Insights on the Emerging Genomic Landscape of CXCR4 in Cancer: A Lesson from WHIM.Vaccines · 2020Review
- Identification of significant genes with prognostic influence in clear cell renal cell carcinoma via bioinformatics analysis.Translational andrology and urology · 2020Article
- The Role of the CXCL12/CXCR4/CXCR7 Chemokine Axis in Cancer.Frontiers in pharmacology · 2020Review
- Emerging role of mTOR in tumor immune contexture: Impact on chemokine-related immune cells migration.Theranostics · 2020Review
- CXCL12 loaded-dermal filler captures CXCR4 expressing melanoma circulating tumor cells.Cell death & disease · 2019Article
- Constitutive and stimulated macropinocytosis in macrophages: roles in immunity and in the pathogenesis of atherosclerosis.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2019Review
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Treatment of metastatic renal cell carcinoma (mRCC) has improved significantly with the advent of agents targeting the mTOR pathway, such as temsirolimus and everolimus. However, their efficacy is thought to be limited by feedback loops and crosstalk with other pathways leading to the development of drug resistance. As CXCR4-CXCL12-CXCR7 axis has been described to have a crucial role in renal cancer; the crosstalk between the mTOR pathway and the CXCR4-CXCL12-CXCR7 chemokine receptor axis has been investigated in human renal cancer cells. In SN12C and A498, the common CXCR4-CXCR7 ligand, CXCL12, and the exclusive CXCR7 ligand, CXCL11, activated mTOR through P70S6K and 4EBP1 targets. The mTOR activation was specifically inhibited by CXCR4 antagonists (AMD3100, anti-CXCR4-12G5 and Peptide R, a newly developed CXCR4 antagonist) and CXCR7 antagonists (anti-CXCR7-12G8 and CCX771, CXCR7 inhibitor). To investigate the functional role of CXCR4, CXCR7 and mTOR in human renal cancer cells, both migration and wound healing were evaluated. SN12C and A498 cells migrated toward CXCL12 and CXCL11; CXCR4 and CXCR7 inhibitors impaired migration and treatment with mTOR inhibitor, RAD001, further inhibited it. Moreover, CXCL12 and CXCL11 induced wound healing while was impaired by AMD3100, the anti CXCR7 and RAD001. In SN12C and A498 cells, CXCL12 and CXCL11 promoted actin reorganization characterized by thin spikes at the cell periphery, whereas AMD3100 and anti-CXCR7 impaired CXCL12/CXCL11-induced actin polymerization, and RAD001 treatment further reduced it. In addition, when cell growth was evaluated in the presence of CXCL12, CXCL11 and mTOR inhibitors, an additive effect was demonstrated with the CXCR4, CXCR7 antagonists and RAD001. RAD001-resistant SN12C and A498 cells recovered RAD001 sensitivity in the presence of CXCR4 and CXCR7 antagonists. In conclusion, the entire axis CXCR4-CXCL12-CXCR7 regulates mTOR signaling in renal cancer cells offering new therapeutic opportunities and targets to overcome resistance to mTOR inhibitors.
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Registered trials
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