Dr. van Golen is Associate Professor in the Department of Biological Sciences at University of Delaware.
The main interest of my laboratory is to understand the biology of Inflammatory breast cancer (IBC). IBC is an extremely aggressive form of breast cancer that is phenotypically unique form of breast cancer. IBC is hallmarked by distinct changes in the skin changes that resemble an infection or mastitis. IBC affects younger women (typically in thier late 20's or early 30's) and progresses rapidly. The rapid progression of the disease is thought to occur because of the propensity of the tumor cells to invade and reside in the dermal lymphatic vessels of the skin overlying the breast.
In 1999 our laboratory found that RhoC GTPase, one member of the Rho family, was overexpressed in inflammatory breast cancer. Later, we found that RhoC over expression was a prognostic marker for metastasis in small breast tumors (<1 cm in size). Since then we have begun to look at how RhoC confers a metastatic phenotype to inflammatory breast cancer and how it interacts with other Rho GTPases. Our studies have expanded to include pancreatic cancer and prostate cancer bone metastasis.
The Rho GTPases comprise a group of 23 small GTP binding proteins that play a significant role in nearly every cellular process. One of the most characterized roles of the Rho proteins is their ability to reorganize the cell cytoskeleton. Signals from the extracellular environment, transduced through growth factor receptors and/or cell adhesion molecules leads to the coordinated activation of Rho proteins and reorganization of the cytoskeleton. In turn, this leads to changes in cells shape, polarity, migratory and invasiveness.
The potent ability of the Rho proteins to affect cell migration and invasion has many implications for the dissemination and spread of cancer and in normal processes such as development and immunity. RhoC GTPase is associated with metastatic spread and thus appears to be a metastatic switch. Interestingly, RhoC is 91% homologous on the protein level to RhoA GTPase, yet the two proteins have completely different functions in the cell. One of our goals is to understand what makes these two GTPases distinct from one another.
A complete understanding of how the Rho proteins, particularly RhoC, can influence progression of a cancer cell to become metastatic is key to the development of anti-metastatic therapies. Aside from IBC our laboratory also has interests in understanding the mechansims underlying prostate cancer skeletal metastasis.