ArticleCell reports2014
The RON receptor tyrosine kinase promotes metastasis by triggering MBD4-dependent DNA methylation reprogramming.
Article in Cell reports, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 49 citations in OpenAlex.
- A network map of macrophage-stimulating protein (MSP) signaling.Journal of cell communication and signaling · 2023Article
- The MST1R/RON Tyrosine Kinase in Cancer: Oncogenic Functions and Therapeutic Strategies.Cancers · 2022Review
- Hotspot ESR1 Mutations Are Multimodal and Contextual Modulators of Breast Cancer Metastasis.Cancer research · 2022Article
- Modeling Metastatic Colonization in a Decellularized Organ Scaffold-Based Perfusion Bioreactor.Advanced healthcare materials · 2022Article
- The MSP-RON axis stimulates cancer cell growth in models of triple negative breast cancer.Molecular oncology · 2020Article
- RON and MET Co-overexpression Are Significant Pathological Characteristics of Poor Survival and Therapeutic Targets of Tyrosine Kinase Inhibitors in Triple-Negative Breast Cancer.Cancer research and treatment · 2020Article
- Dissecting the heterogeneity of the alternative polyadenylation profiles in triple-negative breast cancers.Theranostics · 2020Observational
- Targeting RON receptor tyrosine kinase for treatment of advanced solid cancers: antibody-drug conjugates as lead drug candidates for clinical trials.Therapeutic advances in medical oncology · 2020Review
- When RON MET TAM in Mesothelioma: All Druggable for One, and One Drug for All?Frontiers in endocrinology · 2019Article
- MSP-RON Signaling Is Activated in the Transition From Pancreatic Intraepithelial Neoplasia (PanIN) to Pancreatic Ductal Adenocarcinoma (PDAC).Frontiers in physiology · 2019Article
- Berzosertib (VE-822) inhibits gastric cancer cell proliferation via base excision repair system.Cancer management and research · 2019Article
- Epigenetic silencing of RNF144A expression in breast cancer cells through promoter hypermethylation and MBD4.Cancer medicine · 2018Article
- mTORC1 is a key mediator of RON-dependent breast cancer metastasis with therapeutic potential.NPJ breast cancer · 2018Article
- RON tyrosine kinase mutations in brain metastases from lung cancer.ERJ open research · 2018Article
- Therapeutic Considerations for Ron Receptor Expression in Prostate Cancer.EMS cancer science journal · 2018Article
- For robust big data analyses: a collection of 150 important pro-metastatic genes.Chinese journal of cancer · 2017Review
- Epigenetic determinants of metastasis.Molecular oncology · 2017Review
- The Mbd4 DNA glycosylase protects mice from inflammation-driven colon cancer and tissue injury.Oncotarget · 2016Article
- Distinctive properties of metastasis-initiating cells.Genes & development · 2016Review
- hnRNP A1-mediated translational regulation of the G quadruplex-containing RON receptor tyrosine kinase mRNA linked to tumor progression.Oncotarget · 2016Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Metastasis is the major cause of death in cancer patients, yet the genetic and epigenetic programs that drive metastasis are poorly understood. Here, we report an epigenetic reprogramming pathway that is required for breast cancer metastasis. Concerted differential DNA methylation is initiated by the activation of the RON receptor tyrosine kinase by its ligand, macrophage stimulating protein (MSP). Through PI3K signaling, RON/MSP promotes expression of the G:T mismatch-specific thymine glycosylase MBD4. RON/MSP and MBD4-dependent aberrant DNA methylation results in the misregulation of a specific set of genes. Knockdown of MBD4 reverses methylation at these specific loci and blocks metastasis. We also show that the MBD4 glycosylase catalytic residue is required for RON/MSP-driven metastasis. Analysis of human breast cancers revealed that this epigenetic program is significantly associated with poor clinical outcome. Furthermore, inhibition of Ron kinase activity with a pharmacological agent blocks metastasis of patient-derived breast tumor grafts in vivo.
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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.