Paula J. McKeown-Longo
Muntz Professor and Director
University of Connecticut
Early stages of tumor progression are associated with remodeling of the extracellular matrix. This remodeling includes changes in the levels and organization of adhesive proteins such as fibronectin and vitronectin found in the matrix. These changes in adhesive proteins are thought to be permissive for the increase in cell growth and motility associated with tumor metastasis. Our laboratory is studying the hypothesis that changes in the organization of the extracellular matrix modulate structural linkages between the cell and the matrix which are important to the control of cell growth and motility. Experiments are designed to identify the molecular mechanisms controlling fibronectin and vitronectin-based signal transduction pathways which influence cell cycle progression and cytoskeletal organization. Specific projects in the laboratory include: 1) defining the role of vitronectin in the regulation of pericellular proteolysis; 2) identifying molecular targets important to the regulation of cell cycle progression by fibronectin matrix; and 3) evaluating fibronectin matrix as a potential target for gene therapy in breast cancer.
- Monaghan-Benson, E. and McKeown-Longo, P.J.: uPAR regulates a novel pathway of fibronectin matrix requiring Src dependent transactivation of EGFR. J. Biol. Chem. 281: 9450-9459, 2006.
- Salaszynk, R.M., Zappala, M., Zheng, M., Yu, L., Wilkins-Port, C., and McKeown-Longo, P.J.: The uPA receptor and the somatomedin B region of vitronectin direct the localization of uPA to focal adhesions in microvessel endothelial cells. Matrix Biol. 26: 330-333, 2007.
- Vial, D. and McKeown-Longo, P.J.: PAI-1 stimulates fibronectin matrix assembly in osteosarcoma cells through cross-talk between the alphav/beta5 and alpha5/beta1 integrins. J. Cell Sci. 121: 1661-1670, 2008.
- Monaghan-Benson E, Mastick CC, McKeown-Longo PJ: A dual role for caveolin-1 in the regulation of fibronectin matrix assembly by uPAR. J Cell Sci 121:3693-3703, 2008.
- Ambesi A and McKeown-Longo PJ: Anastellin, the angiostatic fibronectin peptide, is a selective inhibitor of lysophospholipid signaling. Mol Cancer Res 7(2):255-265, 2009.