Caveolae are specific microdomains on cell surface involved in endocytosis, transcytosis and signal transduction. The major structural proteins of caveolae are 22-kDa proteins named caveolins. Recent evidence has suggested that caveolin may function as...
Mechanisms of Metastasis & Therapeutic Response Program (MMTR)
Angiogenesis. Angiogenesis is a process by which new blood vessel develops from pre-existing capillary. This process is tightly regulated both by angiogenesis activators, such as VEGF, FGF and HGF, as well as angiogenesis inhibitors, e.g., angiostatin and endostatin. Although a variety of angiogenesis activators and inhibitors have been identified and characterized, there is very little information on the common target(s) that receives signals from both angiogenic regulators to determine the state of endothelial cells. Recently, we have shown that angiogenesis activators and inhibitors affect the level of caveolin-1 expression. Furthermore, overexpression of caveolin-1 substantially suppresses angiogenic signaling induced by activation of VEGF receptor, hence, suggesting that caveolin might be an intracellular target both for angiogenesis activators and inhibitors. Our laboratory is focusing on the function of caveolin in the regulation of endothelial cell growth and differentiation. There are three general questions we would like to address: 1) what are the molecular mechanisms underlying the reciprocal regulation of caveolin-1 expression by angiogenesis activators (such as VEGF) and angiogenesis inhibitors in endothelial cells? 2) does caveolin-1 affect VEGF receptor signaling pathways? 3) does caveolin-1 play any role in the regulation of angiogenesis?
Cell motility. We have found that during cell migration, caveolin-1 and caveolae polarize at the rear of migrating cells. We hypothesize that when cells are stimulated to migrate, caveolin-1 moves to the rear of a migrating cell in a sequence-specific fashion as a mechanism to sequester it away from signaling proteins that direct cell motility at the leading edge. In deed, we have recently identified a sequence motif that controls caveolin polarity in migrating cells and demonstrated that loss of caveolin polarity impedes cell polarization and directional movement. By using the caveolin depolarization model, we are investigating the role of caveolin in spatial organization of cell signaling, cytoskeleton arrangement and cell migration.