ArticleCancer discovery2021
Blocking Short-Form Ron Eliminates Breast Cancer Metastases through Accumulation of Stem-Like CD4+ T Cells That Subvert Immunosuppression.
Article in Cancer discovery, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 22 citations in OpenAlex.
- Loss of short-form Ron promotes B and T cell cooperation to prevent outgrowth of breast cancer bone metastasis.bioRxiv : the preprint server for biology · 2026Article
- Targeting the tripartite axis of immune-metabolic-spatial crosstalk to overcome therapy resistance in breast cancer.Frontiers in immunology · 2026Review
- Neuro-oncological ventral antigen 1 regulates liver cancer stem cell properties and Lenvatinib resistance via targeting SOX4.Cancer cell international · 2025Article
- MSP-RON signaling in liver pathobiology and as an emerging therapeutic target: a review of the current evidence.Cell communication and signaling : CCS · 2025Review
- miRNA-338-3p influences the liver cancer stem cells and lenvatinib resistance properties by targeting SOX4.Scientific reports · 2025Article
- Review
- NOVA2 regulates the properties of liver cancer stem cells and lenvatinib resistance in hepatocellular carcinoma via the Wnt pathway.Journal of gastrointestinal oncology · 2024Article
- Breast Cancer Immunity: It is TIME for the Next Chapter.Cold Spring Harbor perspectives in medicine · 2024Review
- LncRNA FOXD1-AS1 regulates pancreatic cancer stem cell properties and 5-FU resistance by regulating the miR-570-3p/SPP1 axis as a ceRNA.Cancer cell international · 2024Article
- miRNA-381 regulates renal cancer stem cell properties and sunitinib resistance via targeting SOX4.Biochemistry and biophysics reports · 2023Article
- Myeloid-Derived Suppressor-Cell Dynamics Control Outcomes in the Metastatic Niche.Cancer immunology research · 2023Article
- Review
- Tailoring therapies to counter the divergent immune landscapes of breast cancer.Frontiers in cell and developmental biology · 2023Review
- The MST1R/RON Tyrosine Kinase in Cancer: Oncogenic Functions and Therapeutic Strategies.Cancers · 2022Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Immunotherapy has potential to prevent and treat metastatic breast cancer, but strategies to enhance immune-mediated killing of metastatic tumors are urgently needed. We report that a ligand-independent isoform of Ron kinase (SF-Ron) is a key target to enhance immune infiltration and eradicate metastatic tumors. Host-specific deletion of SF-Ron caused recruitment of lymphocytes to micrometastases, augmented tumor-specific T-cell responses, and nearly eliminated breast cancer metastasis in mice. Lack of host SF-Ron caused stem-like TCF1+ CD4+ T cells with type I differentiation potential to accumulate in metastases and prevent metastatic outgrowth. There was a corresponding increase in tumor-specific CD8+ T cells, which were also required to eliminate lung metastases. Treatment of mice with a Ron kinase inhibitor increased tumor-specific CD8+ T cells and protected from metastatic outgrowth. These data provide a strong preclinical rationale to pursue small-molecule Ron kinase inhibitors for the prevention and treatment of metastatic breast cancer. SIGNIFICANCE: The discovery that SF-Ron promotes antitumor immune responses has significant clinical implications. Therapeutic antibodies targeting full-length Ron may not be effective for immunotherapy; poor efficacy of such antibodies in trials may be due to their inability to block SF-Ron. Our data warrant trials with inhibitors targeting SF-Ron in combination with immunotherapy. This article is highlighted in the In This Issue feature, p. 2945.
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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.