Macrophage-stimulating protein receptor (MST1R) (RON)

The Macrophage-stimulating protein receptor (MST1R), commonly known as RON (Recepteur d'Origine Nantais), is a transmembrane receptor tyrosine kinase belonging to the MET proto-oncogene family (UniProt: Q04912). It is primarily activated by its ligand, macrophage-stimulating protein (MSP), which induces receptor dimerization and autophosphorylation of the C-terminal tail (PubMed: 24531141). This activation triggers downstream signaling through the PI3K/AKT, RAS/MAPK, and STAT3 pathways, which are critical for regulating cell proliferation, survival, and motility (PubMed: 21311539). In various malignancies, including breast, colorectal, and pancreatic cancers, RON is often overexpressed or constitutively active due to alternative splicing, contributing to increased tumor invasiveness and the epithelial-mesenchymal transition (EMT) (PubMed: 23670115). Additionally, RON plays a significant role in the tumor microenvironment by modulating the inflammatory response and the functional polarization of macrophages (PubMed: 11062066). Because of its involvement in tumor progression and metastasis, RON is a target for therapeutic intervention using small-molecule kinase inhibitors, such as cabozantinib, and monoclonal antibodies designed to block ligand binding or induce receptor degradation (ClinicalTrials.gov).

Other names

MST1RCD136PTK8Recepteur d'Origine NantaisMSP receptorProtein-tyrosine kinase 8

Inhibition of the intracellular tyrosine kinase domain, competitive inhibition of ATP binding, blockade of ligand binding via monoclonal antibodies, and induction of receptor internalization and degradation.