Iron Homeostasis Meets RON Kinase in Metastatic Breast Cancer

This proposal investigates the unexplored intersection between iron homeostasis and RON kinase signaling in metastatic breast cancer. Iron availability is known to drive tumorigenesis by enhancing ROS-mediated signaling, while RON (MST1R) is a potent pro-metastatic receptor tyrosine kinase implicated in EMT, immune evasion, and osteoclastogenesis. I hypothesize that intracellular iron is essential for sustaining RON-driven oncogenic pathways, and that iron depletion—via calprotectin or pharmacological chelation—attenuates RON activity, disrupts metastatic phenotypes, and reshapes the tumor immune microenvironment.