In addition to researching epithelial cancer, our lab is also investigating the role of cadherins in brain development, brain tumors, breast cancer and other diseases.
Brain-specific cadherins play important roles in axonal pathfinding and neurite extension. Some research reports suggest that the p120-binding region of these cadherins mediates their effects, while Rho GTPases are known to affect axonal pathfinding and neurite extension. In addition, experiments in knockout animal models suggest that p120 protein family members are important for learning and memory, while Kaiso, the p120-associated transcription factor, plays important roles in brain development and the expression of catecholamine neurotransmitters.
Interestingly, unlike p120, the other p120 family members exhibit a more restricted expression pattern, suggesting that they have specialized functions. These proteins are all expressed in neuronal tissues and are thought to play important roles in spine morphogenesis and neuronal function.
Because all the p120 family members share the ability to affect Rho GTPases, it's also likely that these proteins affect neuronal or glial cell migration associated with normal brain morphogenesis or brain tumor spread.
Led by Dr. Anastasiadis, our lab is testing the latter hypothesis. We're investigating the role of the cadherin/catenin system in human gliomas, a type of brain tumor that's difficult to treat particularly because of the increased tumor spread. We're also investigating the possibility that elevated neuronal cadherin expression in HER2-overexpressing breast cancer cells mediates the increased metastatic potential of these cells to brain.