Adhesion Protiens and Human Glioma
In addition to epithelial cancer, we are also interested in the role of cadherins in brain development and disease. Brain-specific cadherins play important roles in axonal pathfinding and neurite extension. Early 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, recent experiments in knockout animals suggest that p120 family members may be important for learning and memory, while kaiso, the p120-associated transcription factor may play important roles in brain development, as well as the expression of catecholamine neurotransmitters. Finally, we are currently investigating the role of the cadherin/catenin system in human gliomas, a type of tumor that is difficult to treat particularly because of the increased tumor spread. Glioma cells express mesenchymal cadherins and several p120 family members; however, the involvement of these mesenchymal cadherins, p120 or its family members, and β-catenin signaling in the progression and aggressiveness of human gliomas has not been tested to date. We are currently addressing these questions by testing the relevance of cadherins and catenins in the growth and invasiveness of several human glioma cell lines, both in vitro, and following orthotopic brain injection in nude mice.
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