ArticleCancer research2019
S100A10 Is a Critical Mediator of GAS6/AXL-Induced Angiogenesis in Renal Cell Carcinoma.
Article in Cancer research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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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.
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Who cites it
48 citing papers in PubMed, 60 citations in OpenAlex.
- Phase 1b/2 study of batiraxcept alone and in combination with cabozantinib with or without nivolumab for advanced clear cell renal cell carcinoma.The oncologist · 2025Trial
- Systematic identification of p11 as a signaling modulator across the GPCRome.Science advances · 2026Article
- AXL is associated with STAT3 activation in breast cancer.Molecular and clinical oncology · 2026Article
- Identification of serum protein biomarkers for clear cell renal cell carcinoma using patient-derived xenografts.The Journal of clinical investigation · 2026Article
- Tumor-associated macrophages in cancer: from mechanisms to application.Molecular biomedicine · 2025Review
- Development and validation of a prognostic staging system for primary plasma cell leukemia.Journal of hematology & oncology · 2025Article
- The RNA demethylase FTO promotes glutamine metabolism in clear cell renal cell carcinoma through the regulation of SLC1A5.Science advances · 2025Article
- AXL and SRC in clear cell renal cell carcinoma: absence of mutations, rare alternative splicing events, but association of protein expression with poor prognosis.The journal of pathology. Clinical research · 2025Article
- Identification of Molecular Subtypes of Clear-Cell Renal Cell Carcinoma in Patient-Derived Xenografts Using Multi-Omics.Cancers · 2025Article
- Targeting AXL Inhibits the Growth and Metastasis of Prostate Cancer in Bone.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- AXL signaling in cancer: from molecular insights to targeted therapies.Signal transduction and targeted therapy · 2025Review
- Identification of key genes CCL5, PLG, LOX and C3 in clear cell renal cell carcinoma through integrated bioinformatics analysis.Frontiers in molecular biosciences · 2025Article
- Comprehensive analysis of the prognostic and immunological role of cavins in non-small cell lung cancer.BMC cancer · 2024Article
- Targeting of TAMs: can we be more clever than cancer cells?Cellular & molecular immunology · 2024Review
- Elucidating the role of S100A10 in CD8Cell death & disease · 2024Article
- Integrative bioinformatics analysis of miRNA and mRNA expression profiles and identification of associated miRNA-mRNA network in intracranial aneurysms.Non-coding RNA research · 2024Article
- Therapeutic targeting of the functionally elusive TAM receptor family.Nature reviews. Drug discovery · 2024Review
- GAS6/TAM Axis as Therapeutic Target in Liver Diseases.Seminars in liver disease · 2024Article
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Corrections and comments
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
Angiogenesis is a hallmark of cancer that promotes tumor progression and metastasis. However, antiangiogenic agents have limited efficacy in cancer therapy due to the development of resistance. In clear cell renal cell carcinoma (ccRCC), AXL expression is associated with antiangiogenic resistance and poor survival. Here, we establish a role for GAS6/AXL signaling in promoting the angiogenic potential of ccRCC cells through the regulation of the plasminogen receptor S100A10. Genetic and therapeutic inhibition of AXL signaling in ccRCC tumor xenografts reduced tumor vessel density and growth under the renal capsule. GAS6/AXL signaling activated the expression of S100A10 through SRC to promote plasmin production, endothelial cell invasion, and angiogenesis. Importantly, treatment with the small molecule AXL inhibitor cabozantinib or an ultra-high affinity soluble AXL Fc fusion decoy receptor (sAXL) reduced the growth of a pazopanib-resistant ccRCC patient-derived xenograft. Moreover, the combination of sAXL synergized with pazopanib and axitinib to reduce ccRCC patient-derived xenograft growth and vessel density. These findings highlight a role for AXL/S100A10 signaling in mediating the angiogenic potential of ccRCC cells and support the combination of AXL inhibitors with antiangiogenic agents for advanced ccRCC. SIGNIFICANCE: These findings show that angiogenesis in renal cell carcinoma (RCC) is regulated through AXL/S100A10 signaling and support the combination of AXL inhibitors with antiangiogenic agents for the treatment of RCC.
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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.