ArticleJournal of hepatology2021
Ribonuclease 7-driven activation of ROS1 is a potential therapeutic target in hepatocellular carcinoma.
Article in Journal of hepatology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 23 papers.
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23 citing papers in PubMed, 30 citations in OpenAlex.
- The latest progress of personalized drug screening and therapy research for common clinical tumors through the PDX model platform.Journal of pharmaceutical analysis · 2025Review
- Oncogenic cholesterol rewires lipid metabolism in hepatocellular carcinoma via the CSNK2A1-IGF2R Ser2484 axis.Journal of advanced research · 2025Article
- Patient-derived xenograft model: Applications and challenges in liver cancer.Chinese medical journal · 2025Review
- RNase 7 and Th cytokines synergistically increase the secretion of interleukin-6 from keratinocytes.Scientific reports · 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
- Structural basis for the interaction between the Drosophila RTK Sevenless (dROS1) and the GPCR BOSS.Nature communications · 2025Article
- AlphaPPIweb: an integration platform for protein-protein interaction prediction and evaluation.American journal of cancer research · 2025Article
- Novel insight into mechanisms of ROS1 catalytic activation via loss of the extracellular domain.Scientific reports · 2024Article
- Targeting ALK averts ribonuclease 1-induced immunosuppression and enhances antitumor immunity in hepatocellular carcinoma.Nature communications · 2024Article
- A multidimensional platform of patient-derived tumors identifies drug susceptibilities for clinical lenvatinib resistance.Acta pharmaceutica Sinica. B · 2024Article
- Synergistic effect of PARP inhibitor and BRD4 inhibitor in multiple models of ovarian cancer.Journal of cellular and molecular medicine · 2023Article
- Intestinal toxicity to CTLA-4 blockade driven by IL-6 and myeloid infiltration.The Journal of experimental medicine · 2023Article
- Ribonuclease 1 Enhances Antitumor Immunity against Breast Cancer by Boosting T cell Activation.International journal of biological sciences · 2023Article
- Extracellular Vesicles Derived from Human Umbilical Cord Mesenchymal Stem Cells Promote Trophoblast Cell Proliferation and Migration by Targeting TFPI2 in Preeclampsia.Stem cells international · 2023Article
- Structural insights into EphA4 unconventional activation from prediction of the EphA4 and its complex with ribonuclease 1.American journal of cancer research · 2022Article
- Immune classifier-based signatures provide good prognostic stratification and predict the clinical benefits of immune-based therapies for hepatocellular carcinoma.Cancer cell international · 2021Article
- Activated T cell-derived exosomal PD-1 attenuates PD-L1-induced immune dysfunction in triple-negative breast cancer.Oncogene · 2021Article
- Diverse expression patterns of mucin 2 in colorectal cancer indicates its mechanism related to the intestinal mucosal barrier.World journal of gastroenterology · 2021Article
Corrections and comments
- Erratum issued
Authors and funding
19 authors at 3 institutions in 4 countries.
Funding
Abstract
BACKGROUND &
aimsThere are currently limited therapeutic options for hepatocellular carcinoma (HCC), particularly when it is diagnosed at advanced stages. Herein, we examined the pathophysiological role of ROS1 and assessed the utility of ROS1-targeted therapy for the treatment of HCC.
methodsRecombinant ribonucleases (RNases) were purified, and the ligand-receptor relationship between RNase7 and ROS1 was validated in HCC cell lines by Duolink, immunofluorescence, and immunoprecipitation assays. Potential interacting residues between ROS1 and RNase7 were predicted using a protein-protein docking approach. The oncogenic function of RNase7 was analyzed by cell proliferation, migration and invasion assays, and a xenograft mouse model. The efficacy of anti-ROS1 inhibitor treatment was evaluated in patient-derived xenograft (PDX) and orthotopic models. Two independent patient cohorts were analyzed to evaluate the pathological relevance of RNase7/ROS1.
resultsRNase7 associated with ROS1's N3-P2 domain and promoted ROS1-mediated oncogenic transformation. Patients with HCC exhibited elevated plasma RNase7 levels compared with healthy individuals. High ROS1 and RNase7 expression were strongly associated with poor prognosis in patients with HCC. In both HCC PDX and orthotopic mouse models, ROS1 inhibitor treatment markedly suppressed RNase7-induced tumorigenesis, leading to decreased plasma RNase7 levels and tumor shrinkage in mice.
conclusionsRNase7 serves as a high-affinity ligand for ROS1. Plasma RNase7 could be used as a biomarker to identify patients with HCC who may benefit from anti-ROS1 treatment. LAY SUMMARY: Receptor tyrosine kinases are known to be involved in tumorigenesis and have been targeted therapeutically for a number of cancers, including hepatocellular carcinoma. ROS1 is the only such receptor with kinase activity whose ligand has not been identified. Herein, we show that RNase7 acts as a ligand to activate ROS1 signaling. This has important pathophysiological and therapeutic implications. Anti-ROS1 inhibitors could be used to treatment patients with hepatocellular carcinoma and high RNase7 levels.
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