The development of metastatic disease in cancer patients remains a major challenge for treatment due to our limited understanding of the processes by which tumor cells spread throughout the body. The process of metastasis requires that cells can crawl and invade through normal tissues. This proposal focuses on our unexpected discovery of a new regulator of a cancer cell’s ability to crawl and invade. This regulator, called TPP1, has never been shown to have this function. However, by studying how TPP1 is changed in families with inherited cancers, we learned that TPP1 has multiple abilities to control tumor cells. Importantly, we do not yet know how TPP1 controls a cancer cell’s ability to move and invade. This pilot grant will support our paradigm-shifting studies that will begin to reveal how TPP1 controls the behaviors of cancer cells that are associated with highly aggressive disease. We will focus our studies on colon and breast cancer as well as melanoma and will learn whether TPP1 controls tumor cell movement and invasion in diverse types of cancer. We will also begin uncovering how TPP1 contributes to metastatic behaviors with the ultimate intent of determining if it may be a new target for drug development.