ArticleMolecular cancer2010
Deletion or insertion in the first immunoglobulin-plexin-transcription (IPT) domain differentially regulates expression and tumorigenic activities of RON receptor Tyrosine Kinase.
Article in Molecular cancer, 2010. 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, 58 citations in OpenAlex.
- Plexin A2 regulated the metastasis in breast cancer through MCM7.BMC cancer · 2026Article
- MSP-RON signaling in liver pathobiology and as an emerging therapeutic target: a review of the current evidence.Cell communication and signaling : CCS · 2025Review
- MAGOH promotes gastric cancer progression via hnRNPA1 expression inhibition-mediated RONΔ160/PI3K/AKT signaling pathway activation.Journal of experimental & clinical cancer research : CR · 2024Article
- Review
- Review
- RON in hepatobiliary and pancreatic cancers: Pathogenesis and potential therapeutic targets.World journal of gastroenterology · 2021Review
- MET and RON receptor tyrosine kinases in colorectal adenocarcinoma: molecular features as drug targets and antibody-drug conjugates for therapy.Journal of experimental & clinical cancer research : CR · 2020Review
- Hypoxia-induced alternative splicing: the 11th Hallmark of Cancer.Journal of experimental & clinical cancer research : CR · 2020Review
- Article
- Splice variants of the extracellular region of RON receptor tyrosine kinase in lung cancer cell lines identified by PCR and sequencing.BMC cancer · 2017Article
- Monoclonal antibody Zt/g4 targeting RON receptor tyrosine kinase enhances chemosensitivity of bladder cancer cells to Epirubicin by promoting G1/S arrest and apoptosis.Oncology reports · 2017Article
- Strategies of targeting the extracellular domain of RON tyrosine kinase receptor for cancer therapy and drug delivery.Journal of cancer research and clinical oncology · 2016Review
- A novel protein isoform of the RON tyrosine kinase receptor transforms human pancreatic duct epithelial cells.Oncogene · 2016Article
- Identification of a novel MET mutation in high-grade glioma resulting in an auto-active intracellular protein.Acta neuropathologica · 2015Article
- Variant RONΔ160 of the RON receptor tyrosine kinase promotes the growth and invasion in vitro and in vivo in gastric cancer cell lines.Cancer cell international · 2015Article
- Structural basis for the binding specificity of human Recepteur d'Origine Nantais (RON) receptor tyrosine kinase to macrophage-stimulating protein.The Journal of biological chemistry · 2014Article
- Pathogenesis of RON receptor tyrosine kinase in cancer cells: activation mechanism, functional crosstalk, and signaling addiction.Journal of biomedical research · 2013Review
- MSP-RON signalling in cancer: pathogenesis and therapeutic potential.Nature reviews. Cancer · 2013Review
- Plexin structures are coming: opportunities for multilevel investigations of semaphorin guidance receptors, their cell signaling mechanisms, and functions.Cellular and molecular life sciences : CMLS · 2012Review
- Crystal structure of the Sema-PSI extracellular domain of human RON receptor tyrosine kinase.PloS one · 2012Article
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundActivation of the RON receptor tyrosine kinase, a member of the c-MET family, regulates tumorigenic phenotypes. The RON extracellular domains are critical in regulating these activities. The objective of this study was to determine the role of the first IPT domain in regulating RON-mediated tumorigenic activities and the underlying mechanisms.
resultsTwo RON variants, RON160 and RONE5/6in with deletion and insertion in the first IPT domain, respectively, were molecularly cloned. RON160 was a splicing variant generated by deletion of 109 amino acids encoded by exons 5 and 6. In contrast, RONE5/6in was derived from a transcript with an insertion of 20 amino acids between exons 5 and 6. Both RON160 and RONE5/6in were proteolytically matured into two-chain receptor and expressed on the cell surface. RON160 was constitutively active with tyrosine phosphorylation. However, activation of RONE5/6in required ligand stimulation. Deletion resulted in the resistance of RON160 to proteolytic digestion by cell associated trypsin-like enzymes. RON160 also resisted anti-RON antibody-induced receptor internalization. These features contributed to sustained intracellular signaling cascades. On the other hand, RONE5/6in was highly susceptible to protease digestion, which led to formation of a truncated variant known as RONp110. RONE5/6in also underwent rapid internalization upon anti-RON antibody treatment, which led to signaling attenuation. Although ligand-induced activation of RONE5/6in partially caused epithelial to mesenchymal transition (EMT), it was RON160 that showed cell-transforming activities in cell focus formation and anchorage-independent growth. RON160-mediated EMT is also associated with increased motile/invasive activity.
conclusionsAlterations in the first IPT domain in extracellular region differentially regulate RON mediated tumorigenic activities. Deletion of the first IPT results in formation of oncogenic variant RON160. Enhanced degradation and internalization with attenuated signaling cascades could be the mechanisms underlying non-tumorigenic features of RONE5/6in.
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