Grant: Project Grant

One of the biggest challenges in cancer treatment is preventing metastasis, the process by which cells from a tumor spread to other sites in the body and form secondary tumors that cause most cancer deaths. Tumor cells have acquired special properties that allow them to spread; notably the ability to invade tissues. Developing treatments to prevent cancer cell spreading requires better understanding of the mechanisms that enable this invasive ability. Cancer cell invasion is mediated by cell structures called invadopodia. These organized structures protrude from the cell body and produce enzymes that degrade the surroundings, clearing a path for the tumor cell to move. Growing knowledge of the molecular regulation and biology of invadopodia has been informed by research into similar but clearly distinct cell structures that regulate normal cell movement. In normal cells, related but non-invasive structures called focal adhesions (FAs) control interactions with their surroundings and cell migration. We discovered that a molecule called PTPa is present in FAs and plays key roles in the molecular communication that regulates FA function and normal cell movement. In our proposed research we will identify interactions between PTPa and other FA molecules, and elucidate how the outcomes of these interactions control cell movement. In parallel, we will investigate the roles of PTPa in cancer cell invadopodia, using breast and colorectal cancer cell lines as models. Our findings suggest that PTPa is involved in regulating the formation of these structures. We will investigate this, and determine if PTPa is required for invasive activity of invadopodia and how PTPa co-ordinates with other molecules to control this. Our research will provide new knowledge of the molecular connections and functions of PTPa that promote normal cell movement and tumor cell invasion. This will increase opportunities to develop targeted molecular therapies to combat cancer metastasis.