The MST1R/RON Tyrosine Kinase in Cancer: Oncogenic Functions and Therapeutic Strategies

Abstract

The MST1R/RON receptor tyrosine kinase is a homologue of the more well-known MET receptor. Like MET, RON orchestrates cell signaling pathways that promote oncogenesis and enable cancer cell survival; however, it has a more unique role in the regulation of inflammation. RON was originally described as a transmembrane receptor expressed on tissue resident macrophages and various epithelial cells. RON is overexpressed in a variety of cancers and its activation modifies multiple signaling pathways with resultant changes in epithelial and immune cells which together modulate oncogenic phenotypes. While several RON isoforms have been identified with differences in structure, activation, and pathway regulation, increased RON expression and/or activation is consistently associated with worse outcomes. Tyrosine kinase inhibitors targeting RON have been developed, making RON an actionable therapeutic target.

The miR-141/200c-STAT4 Axis Contributes to Leukemogenesis by Enhancing Cell Proliferation in T-PLL

“…Unsupervised hierarchical clustering revealed a distinct transcriptome in the 'high miR-141/200c' cohort, consisting of 356 differentially expressed genes discriminating between the 'high' and 'low' miR-141/200c cluster (Figure 1c, Table S2). 'High miR-141/200c'-expressing T-PLL cells showed an elevated expression of genes involved in oncogenesis, such as the immunemodulatory receptor tyrosin kinase MST1R (fc = 8.71, FDR < 0.0001) [29] and the chemokine CCL25 (fc = 59.77, FDR < 0.0001) [30], as well as genes contributing to cell cycle progression such as CCNA1 (fc = 51.14, FDR < 0.0001) [31]. As miR-mediated regulation of cellular processes is based on the induction of low-level changes of mRNA abundances affecting a larger cohort of genes rather than one single factor, we conducted gene set enrichment (GSEA) analyses using the complete list of fcs of all protein-coding genes characterizing the 'high miR-141/200c' cohort (Figure 1d).…”

NEST: Spatially-mapped cell-cell communication patterns using a deep learning-based attention mechanism

“…Plexins are known for their key role in tumor CCC, tumor growth, migration, and metastasis. Semaphorins are the main ligands of the Plexin receptors; however, some plexins can also form complexes with other tyrosine-kinase receptors, such as the hepatocyte growth factor receptor (HGFR) encoded by MET 65 and RON encoded by MST1R 66 . NEST reported a PLXNB2 - MET / MSTR1 CCC pattern that is favored in Classical over Basal areas of the tumor.…”

Exploring Splicing Modulation as an Innovative Approach to Combat Pancreatic Cancer: SF3B1 Emerges as a Prognostic Indicator and Therapeutic Target

“…Control over migration mechanisms is governed not only by transcription factors but also by alternatively spliced transcripts such as ∆RON 57 . RON, a receptor with tyrosine-kinase activity, is a member of the MET family, exerting a crucial function in the oncogenesis of numerous tumors in humans 42 , 58 - 61 . RON is detected in about 90% of PDAC samples and has been documented to have a pivotal role in the tumorigenesis and progression 62 .…”