ArticleOncogene2016
A novel protein isoform of the RON tyrosine kinase receptor transforms human pancreatic duct epithelial cells.
Article in Oncogene, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 33 citations in OpenAlex.
- Long Noncoding RNA DGUOK-AS1 Promotes Bladder Cancer Progression by Enhancing EFTUD2 Stability.Cancer research and treatment · 2026Article
- Article
- MSP-RON signaling in liver pathobiology and as an emerging therapeutic target: a review of the current evidence.Cell communication and signaling : CCS · 2025Review
- Article
- Review
- The MST1R/RON Tyrosine Kinase in Cancer: Oncogenic Functions and Therapeutic Strategies.Cancers · 2022Review
- Interrelationship between miRNA and splicing factors in pancreatic ductal adenocarcinoma.Epigenetics · 2022Review
- A potential signaling axis between RON kinase receptor and hypoxia-inducible factor-1 alpha in pancreatic cancer.Molecular carcinogenesis · 2021Article
- PRMT5: An Emerging Target for Pancreatic Adenocarcinoma.Cancers · 2021Review
- The effect of splicing MST1R in gastric cancer was enhanced by lncRNA FENDRR.Experimental and therapeutic medicine · 2021Article
- Drivers of Gene Expression Dysregulation in Pancreatic Cancer.Trends in cancer · 2021Review
- SF3B1 modulators affect key genes in metastasis and drug influx: a new approach to fight pancreatic cancer chemoresistance.Cancer drug resistance (Alhambra, Calif.) · 2021Article
- The HNRNPA2B1-MST1R-Akt axis contributes to epithelial-to-mesenchymal transition in head and neck cancer.Laboratory investigation; a journal of technical methods and pathology · 2020Article
- 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
- Therapeutic efficacy of a novel humanized antibody-drug conjugate recognizing plexin-semaphorin-integrin domain in the RON receptor for targeted cancer therapy.Journal for immunotherapy of cancer · 2019Article
- Therapeutic efficacy, pharmacokinetic profiles, and toxicological activities of humanized antibody-drug conjugate Zt/g4-MMAE targeting RON receptor tyrosine kinase for cancer therapy.Journal for immunotherapy of cancer · 2019Article
- MSP-RON Signaling Is Activated in the Transition From Pancreatic Intraepithelial Neoplasia (PanIN) to Pancreatic Ductal Adenocarcinoma (PDAC).Frontiers in physiology · 2019Article
- Genome-Wide Profiling of Prognostic Alternative Splicing Pattern in Pancreatic Cancer.Frontiers in oncology · 2019Article
- mTORC1 is a key mediator of RON-dependent breast cancer metastasis with therapeutic potential.NPJ breast cancer · 2018Article
- The Cancer Spliceome: Reprograming of Alternative Splicing in Cancer.Frontiers in molecular biosciences · 2018Review
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
The MST1R gene is overexpressed in pancreatic cancer producing elevated levels of the RON tyrosine kinase receptor protein. While mutations in MST1R are rare, alternative splice variants have been previously reported in epithelial cancers. We report the discovery of a novel RON isoform discovered in human pancreatic cancer. Partial splicing of exons 5 and 6 (P5P6) produces a RON isoform that lacks the first extracellular immunoglobulin-plexin-transcription domain. The splice variant is detected in 73% of xenografts derived from pancreatic adenocarcinoma patients and 71% of pancreatic cancer cell lines. Peptides specific to RON P5P6 detected in human pancreatic cancer specimens by mass spectrometry confirm translation of the protein isoform. The P5P6 isoform is found to be constitutively phosphorylated, present in the cytoplasm, and it traffics to the plasma membrane. Expression of P5P6 in immortalized human pancreatic duct epithelial (HPDE) cells activates downstream AKT, and in human pancreatic epithelial nestin-expressing cells, activates both the AKT and MAPK pathways. Inhibiting RON P5P6 in HPDE cells using a small molecule inhibitor BMS-777607 blocked constitutive activation and decreased AKT signaling. P5P6 transforms NIH3T3 cells and induces tumorigenicity in HPDE cells. Resultant HPDE-P5P6 tumors develop a dense stromal compartment similar to that seen in pancreatic cancer. In summary, we have identified a novel and constitutively active isoform of the RON tyrosine kinase receptor that has transforming activity and is expressed in human pancreatic cancer. These findings provide additional insight into the biology of the RON receptor in pancreatic cancer and are clinically relevant to the study of RON as a potential therapeutic target.
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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.