J. Thomas Parsons, PhD
Role of cell adhesion signaling in cell migration and cancer cell metastasis
Signal transduction cascades initiated by growth factors and extracellular matrix-integrin interactions regulate cell adhesion and migration, cell growth and differentiation, and cancer cell growth and metastasis. Research in the J. T. Parsons laboratory focus on the role of focal adhesion kinase (FAK) in mediating signals from the extracellular matrix through integrin receptors. FAK and its interacting partners play a central role in propagating signals that regulate cell motility. In addition, expression of FAK is up regulated in a large number of different cancers, being expressed at high levels in primary invasive cancers and metastatic lesions. Using "real time" imaging models coupled with biochemical analysis of adhesion signaling pathways, the role of FAK and adhesion signaling pathways is being studied in normal and cancer cells. This includes the physiological significance of increased expression of FAK in tumor cells. Using siRNA approaches to suppress FAK expression or expression of dominant negative forms of FAK, it has been established that FAK expression is required for growth of several prostate and breast cancer cell lines, both in vitro growth and in xenograph models. A second area of research focuses on the novel actin binding protein, Cortactin. Cortactin, often upregulated in human tumors, regulates actin-dependent mechanisms important for membrane ruffling, endocytosis and cell motility. Cortactin binds to and regulates the Arp2/3 complex, a multi-protein complex that regulates filopodia and lamellipodia formation by promoting "branched actin polymerization". Cortactin also binds to cell surface receptor complexes, targeting these complexes to sites of dynamic actin rearrangement. Ongoing efforts are focused on developing novel approaches to both define and eventually exploit, inhibitors of adhesion signaling as potential therapeutic drugs for cancer metastasis. The lab collaborates with Rick Horwitz as Co-PI on the NIGMS Glue grant; and co-author on several reviews and papers. Collaborations with Sally Parsons includes Co-edited issue of ONCOGENE devoted to Src Family Kinases. Parsons also co-authored papers with Michael Weber. Parsons is also a co-P.I. with Dan Theodorescu on Project 1 of Theodorescu's recently funded NCI prostate cancer program project. In addition, David Brautican and Ian Macara are members of the Parsons NCI Program Project, year 19. Usage of CC research cores includes the Lymphocyte Core that stores all of their monoclonal antibodies and produces antibodies for the lab. The Biomolecular research Core does all of the MS analysis and provides addition DNA sequencing and peptide synthesis support. The FACS Core provides all of our FACS analysis. Finally, the Transgenic Mouse Core made 6 transgenic mice and two knockout strains of mice.