ArticleNature communications2021
Human ribonuclease 1 serves as a secretory ligand of ephrin A4 receptor and induces breast tumor initiation.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 30 citations in OpenAlex.
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- Anti-galectin-9 therapy synergizes with EGFR inhibition to reprogram the tumor microenvironment and overcome immune evasion.Journal for immunotherapy of cancer · 2025Article
- RNase1-driven ALK-activation is an oncogenic driver and therapeutic target in non-small cell lung cancer.Signal transduction and targeted therapy · 2025Article
- Ribonuclease 1 Induces T-Cell Dysfunction and Impairs CD8Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- RNASET2 Deficiency Induces Hepatocellular Carcinoma Metastasis through Cholesterol-Triggered MET Activation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- AlphaPPIweb: an integration platform for protein-protein interaction prediction and evaluation.American journal of cancer research · 2025Article
- Identification of a Novel Intracellular Function of the Secreted Ribonuclease RNASE1 in Inhibiting Gene Expression.Molecular and cellular biology · 2025Article
- Molecular heterogeneity of quiescent melanocyte stem cells revealed by single-cell RNA-sequencing.Pigment cell & melanoma research · 2024Article
- Ephs in cancer progression: complexity and context-dependent nature in signaling, angiogenesis and immunity.Cell communication and signaling : CCS · 2024Review
- Targeting ALK averts ribonuclease 1-induced immunosuppression and enhances antitumor immunity in hepatocellular carcinoma.Nature communications · 2024Article
- Development and validation of a disulfidptosis and disulfide metabolism-related risk index for predicting prognosis in lung adenocarcinoma.Cancer cell international · 2024Article
- Eph receptors and ephrins in cancer progression.Nature reviews. Cancer · 2024Review
- RNASE4 promotes malignant progression and chemoresistance in hypoxic glioblastoma via activation of AXL/AKT and NF-κB/cIAPs signaling pathways.American journal of cancer research · 2024Article
- Lipidation and PEGylation Strategies to Prolong theEuropean journal of medicinal chemistry · 2023Article
- Comprehensive Analysis of Purine-Metabolism-Related Gene Signature for Predicting Ovarian Cancer Prognosis, Immune Landscape, and Potential Treatment Options.Journal of personalized medicine · 2023Article
- Ribonuclease 1 Enhances Antitumor Immunity against Breast Cancer by Boosting T cell Activation.International journal of biological sciences · 2023Article
- Macrophages Are a Double-Edged Sword: Molecular Crosstalk between Tumor-Associated Macrophages and Cancer Stem Cells.Biomolecules · 2022Review
- Emerging biological functions of ribonuclease 1 and angiogenin.Critical reviews in biochemistry and molecular biology · 2022Review
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Authors and funding
30 authors at 6 institutions in 4 countries.
Funding
Abstract
Human ribonuclease 1 (hRNase 1) is critical to extracellular RNA clearance and innate immunity to achieve homeostasis and host defense; however, whether it plays a role in cancer remains elusive. Here, we demonstrate that hRNase 1, independently of its ribonucleolytic activity, enriches the stem-like cell population and enhances the tumor-initiating ability of breast cancer cells. Specifically, secretory hRNase 1 binds to and activates the tyrosine kinase receptor ephrin A4 (EphA4) signaling to promote breast tumor initiation in an autocrine/paracrine manner, which is distinct from the classical EphA4-ephrin juxtacrine signaling through contact-dependent cell-cell communication. In addition, analysis of human breast tumor tissue microarrays reveals a positive correlation between hRNase 1, EphA4 activation, and stem cell marker CD133. Notably, high hRNase 1 level in plasma samples is positively associated with EphA4 activation in tumor tissues from breast cancer patients, highlighting the pathological relevance of the hRNase 1-EphA4 axis in breast cancer. The discovery of hRNase 1 as a secretory ligand of EphA4 that enhances breast cancer stemness suggests a potential treatment strategy by inactivating the hRNase 1-EphA4 axis.
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