Grant: Project Grant

Breast cancer becomes life-threatening when it spreads (metastasizes) to other organs such as bone and lung. Treatments that stop spread are limited because many of the signaling pathways that cancer cells use to migrate and invade are also important for healthy tissues. This makes it hard to block these pathways safely. Our team discovered a new protein called GREP1 (Glycine-Rich Extracellular Protein-1). GREP1 is released (secreted) by breast cancer cells and is much more abundant in aggressive, metastatic tumors than in normal adult tissues. GREP1 acts like a "switch" on the outside of the cell by binding to a surface receptor called integrin. When GREP1 binds this receptor, it turns on signals that help cancer cells survive, move, invade, and spread. Importantly, in our early studies, removing GREP1 or blocking it with antibodies reduces cancer cell invasion. In this project, we will: (1) confirm exactly how GREP1 binds integrin and test its effects in more realistic models, including a bone-on-a-chip system that mimics how cancer spreads to bone; (2) map the key signaling steps that GREP1 triggers inside the cell; and (3) test new anti-GREP1 antibody treatments to see if blocking GREP1 can slow or prevent breast cancer spread. If successful, this research will establish GREP1 as a promising new, cancer-selective target and lay the groundwork for safer therapies to prevent metastatic breast cancer.