Mst1r, also known as RON (recepteur d'origine nantais), is a receptor tyrosine kinase homologous to the MET receptor. It orchestrates cell signaling pathways promoting oncogenesis and cancer cell survival, and uniquely regulates inflammation. RON is expressed on tissue resident macrophages and various epithelial cells [1].

In pancreatic cancer, using genetically engineered mouse models, Mst1r overexpression accelerated pancreatic carcinogenesis, increasing acinar-ductal metaplasia (ADM), pancreatic intraepithelial neoplasia (PanIN) progression, and accumulation of MRC1 +, Arg + macrophages. Conversely, absence of functional Mst1r kinase slowed PanIN initiation, reduced tumor size, prolonged survival, and decreased tumor-associated macrophage content. Suppression of Mst1 (Mst1r ligand) expression in orthotopic models led to reduced tumor size, macrophage polarization changes, and enhanced T cell infiltration [2].

In breast cancer, high Mst1R expression was associated with poorer relapse-free survival, overall survival, and metastatic progression, and was not associated with tumor stage, nodal status, or subtype [3].

In conclusion, Mst1r plays a crucial role in cancer development, especially in pancreatic and breast cancer. Mouse models, especially those with Mst1r knockout or manipulation of its ligand, have revealed its functions in promoting cancer progression, macrophage regulation, and its potential as a prognostic biomarker. This highlights the significance of Mst1r in understanding cancer biology and developing targeted therapies.