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.
- Shinde, A.V., Kelsh, R., Peters, J.H., Sekiguchi, K., Van De Water, L., and McKeown-Longo, P.J.: The alpha4/beta1 integrin and the EDA domain of fibronectin regulate a profibrotic phenotpye in dermal fibroblasts. Matrix Biol. 2014 Nov. 26. pii:S0945-053X(14)00216-0. doi: 10.1016/j.matbio.2014.11.004 [Epub ahead of print]
- Kelsh, R., You, R., Horzempa, C., Zheng, M., and McKeown-Longo, P.J.: Regulation of the innate immune response by fibronectin: synergism between the III-1 and EDA domains. PLoS One 9:e102974, 2014.
- Ambesi, A. and McKeown-Longo, P.J.: Conformational remodeling of the fibronectin matrix selectively regulates BEGF signaling. J. Cell Sci. 127:3805-3816, 2014.
- Kelsh, R.M. and McKeown-Longo, P.J.: Topographical changes in extracellular matrix: Activation of TLR4 signaling and solid tumor progression. Trends Cancer Res. 9:1-13, 2013.
- Vial, D. and McKeown-Longo, P.J.: Epidermal growth factor (EGF) regulates alpha5/beta1 integrin activation state in human cancer cell lines through p90RSK-dependent phosphorylation of filamin A. J. Biol. Chem. 287:40371-40380, 2012.
- Zheng, M., Jones, D.M., Horzempa, C., Prasad, A., and McKeown-Longo, P.J.: The first type III domain of fibronectin is associated with the expression of cytokines within the lung tumor microenvironment. J. Cancer 2:478-483, 2011.
- You, R., Zheng, M. and McKeown-Longo, P.J.: The first type III repeat in fibronectin activates an inflammatory pathway in dermal fibroblasts. J. Biol. Chem. 285:36255-36259, 2010.
- You, R., Klein, R.M., Zheng, M., and McKeown-Longo, P.J.: Regulation of p38 MAP kinase by anastellin is independent of anastellin's effect on matrix fibronectin. Matrix Biol. 28:101-109, 2009.
- Ambesi, A. and McKeown-Longo, P.J.: Anastellin, the angiostatic fibronectin peptide, is a selective inhibitor of lysophospholipid signaling. Mol. Cancer Res. 7:255-265, 2009.
- Monaghan-Benson, E., Mastick, C.C., and McKeown-Longo, P.J.: A dual role for caveolin-1 in the regulation of fibronectin matrix assembly by uPAR. J. Cell Sci. 121:3693-3703, 2008.