Requirement of Both Tyrosine Residues 1330 and 1337 in the C-Terminal Tail of the RON Receptor Tyrosine Kinase for Epithelial Cell Scattering and Migration

2000 ◽  
Vol 267 (2) ◽  
pp. 669-675 ◽  
Author(s):  
Z.-Q. Xiao ◽  
Y.-Q. Chen ◽  
M.-H. Wang
Keyword(s):  
Epithelial Cell ◽  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
Tyrosine Residues ◽  
Cell Scattering ◽  
Ron Receptor ◽  
And Migration

scholarly journals Targeting RON receptor tyrosine kinase for treatment of advanced solid cancers: antibody–drug conjugates as lead drug candidates for clinical trials

2020 ◽  
Vol 12 ◽  
pp. 175883592092006
Author(s):  
Hang-Ping Yao ◽  
Sreedhar Reddy Suthe ◽  
Xiang-Min Tong ◽  
Ming-Hai Wang
Keyword(s):  
Clinical Trials ◽  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
Targeted Therapeutics ◽  
Antibody Drug Conjugates ◽  
Drug Candidates ◽  
Drug Conjugates ◽  
Ron Receptor ◽  
Antibody Drug

The recepteur d’origine nantais (RON) receptor tyrosine kinase, belonging to the mesenchymal-to-epithelial transition proto-oncogene family, has been implicated in the pathogenesis of cancers derived from the colon, lung, breast, and pancreas. These findings lay the foundation for targeting RON for cancer treatment. However, development of RON-targeted therapeutics has not gained sufficient attention for the last decade. Although therapeutic monoclonal antibodies (TMABs) targeting RON have been validated in preclinical studies, results from clinical trials have met with limited success. This outcome diminishes pharmaceutical enthusiasm for further development of RON-targeted therapeutics. Recently, antibody–drug conjugates (ADCs) targeting RON have drawn special attention owing to their increased therapeutic activity. The rationale for developing anti-RON ADCs is based on the observation that cancer cells are not sufficiently addicted to RON signaling for survival. Thus, TMAB-mediated inhibition of RON signaling is ineffective for clinical application. In contrast, anti-RON ADCs combine a target-specific antibody with potent cytotoxins for cancer cell killing. This approach not only overcomes the shortcomings in TMAB-targeted therapies but also holds the promise for advancing anti-RON ADCs into clinical trials. In this review, we discuss the latest advancements in the development of anti-RON ADCs for targeted cancer therapy including drug conjugation profile, pharmacokinetic properties, cytotoxic effect in vitro, efficacy in tumor models, and toxicological activities in primates.

scholarly journals MicroRNA Expression Profiling of Lung Cancer with Differential Expression of the RON Receptor Tyrosine Kinase

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Huilin Ou ◽  
Keda Chen ◽  
Hongcheng Wu
Keyword(s):  
Lung Cancer ◽  
Tyrosine Kinase ◽  
Cell Lung Cancer ◽  
Receptor Tyrosine Kinase ◽  
Mapk Signaling ◽  
Differentially Expressed ◽  
Biological Behavior ◽  
Cancer Type ◽  
Mesenchymal Transition ◽  
Ron Receptor

Background. The Ron receptor tyrosine kinase (RON) can act as a protooncogene and may play a prominent role in the initiation and development of lung cancer. microRNAs (miRNA) are master regulators of gene expression through direct or indirect regulation, and impact all aspects of cell biology. Methods. Nonsmall-cell lung cancer (NSCLC) samples and small-cell lung cancer (SCLC) were stratified based on RON expression to identify miRNA profiles associated with RON expression levels, differentially expressed miRNA regulated by RON were screened out, and their biological behavior was analyzed. Results. miRNA expression was most significantly affected by cancer type, and we found 85 miRNAs that were significantly differentially expressed between NSCLC and SCLC. There were 46 miRNAs differentially expressed between high RON expressing NSCLC compared to low RON expressing NSCLC. Biological processes and pathways found to be significantly influenced by RON expression included epithelial-mesenchymal transition (EMT) and activation of the PI3K-Akt and MAPK signaling pathways. Conclusions. These data may provide the basis for a novel strategy to characterize lung cancer by RON expression and microRNA genotyping.

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