Our laboratory is interested in elucidating the role of cadherins and their intracellular binding partners, the catenins, in human cancer. In particular, we are investigating cadherin-mediated signaling events that suppress cell motility and invasiveness and promote the reorganization of the actin cytoskeleton. A central player in these events is p120 catenin, a cadherin-binding partner that is thought to turn adhesion 'on' or 'off' depending on its phosphorylation status. Our observation that cadherin-unbound p120 inhibits the activity of RhoA, linked cadherin-mediated adhesion with Rho GTPases, a family of molecular switches that play instrumental roles in the organization of the cytoskeleton and cell motility. We are testing the mechanism by which p120 affects different Rho GTPases and the potential role of these effects in cell-cell adhesion, motility/invasiveness, and tumor metastasis. Our goal is to translate this better understanding of cell motility and invasiveness into targeted therapeutic treatments that block invasiveness and metastasis in cancer patients. Finally, we are also investigating the interaction of p120 with microtubules and kinesin. We postulate that the association of p120 with microtubule filaments mediates p120 delivery to its sites of action and promotes either cell-cell adhesion or cell motility.
In addition to epithelial tumors, we are also interested in the role of the cadherin-catenin complex in the progression of brain tumors. Cadherins and catenins are thought to play an important role in synaptogenesis and neuronal plasticity. However, deregulation of the cadherin-catenin complex may also promote brain tumor progression and the acquisition of an invasive phenotype.
For a more detailed description of current research projects, please visit our lab's website.