CANCER FOCUS
Our studies on the role of the dynamin family and associated proteins in cellular trafficking processes has significant cancer relevance.
Receptor Down-regulation:
We and others have demonstrated that dynamin function is essential for clathrin-mediated endocytosis of receptors and for internalization of caveolae. Both of these endocytic compartments are involved in regulating cell growth and neoplastic potential through attenuation of receptor signaling cascades. Defining the role of the dynamins and other proteins in the endocytic machinery is a major focus of this laboratory.
Cell Migration and Metastasis:
Many types of cancers spread to distant organs in the body by migration through blood vessel walls. The mechanisms of tumor cell adhesion, motility and invasion are extremely complex and essential components of the metastatic process. We were the first to show an interaction between dynamin and a component of the actin cytoskeleton, cortactin, which is an actin binding, src-substrate protein. The concept of a src-substrate, actin remodeling protein binding to a mechoenzyme such as dynamin is attractive. Further, these proteins colocalize in the leading lamellipodia of migrating tumor cells and appear to be essential in cytoskeletal reorganization to facilitate migration. How these proteins interact to regulate cytoskeletal and membrane dynamics during tumor cell migration is a central focus of our group.
Mitochondrial Dynamics and Programmed Cell Death:
It is well established that mitochondria play a role in regulated cell death cascades and apoptosis. A dynamin like protein (DLP1) that we and others have identified in mammalian cells appears to regulate fission of this important organelle through its mechanochemical properties. DLP1 shares 38% homology with conventional dynamins and also lacks the proline rich tail. Further, DLP1 has recently been implicated in mitochondrial-based apoptosis. The concept of this mechanoenzyme working to model mitochondrial membranes to regulate the release of apoptotic factors is an attractive model.
