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Regulation of cell migration by focal adhesion adapter proteins and their role in cancer cell metastasis.
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The dynamic adhesion of cells to their surrounding extracellular matrix provides many of the environmental cues necessary for controlling cell migration and cell shape, survival, proliferation and differentiation. These fundamental events regulate an organism’s normal development, maintenance and recovery from injury and infection. Defects in the signaling pathways associated with cell adhesion provide the basis for cell transformation and cancer cell metastasis, various developmental defects and cardiovascular disease.
My lab uses a multi-faceted approach combining biochemistry, cell and molecular biology and various high-end microscopy techniques along with mouse tumor models to determine the molecular organization of the proteins that are involved in cell adhesion and thereby understand how they each contribute to cell behavior in vivo. We are particularly interested in characterizing the function of the molecular scaffold/adapter proteins Paxillin and Hic-5 during tumor cell migration and invasion. We have found that these multi-domain proteins bind numerous structural and signaling proteins including kinases, phosphatases and Rho family GTPase regulators and effectors. We hypothesize that it is through these various interactions that the cell coordinates intracellular signaling and cytoskeletal reorganization to regulate cell adhesion, migration and tumor invasion.
Turner, C.E., (2000) Paxillin and focal adhesion signaling. Nature Cell Biol., 2 E231-6.
Brown, M.C. and Turner, C.E. (2004) Paxillin-Adapting to change. Physiol. Revs. 84, 1315-1339.
Deakin, N.O., and Turner, C.E. Paxillin Comes of Age. (2008) J. Cell Sci 121, 2435-2444.
Deakin, N.O. and Turner. C.E. (2011) Paxillin and Hic-5 cooperate to regulate breast cancer cell plasticity, invasion and metastasis. Mol. Biol Cell 22 327-341.
Pignatelli, J., Tumbarello, D.A., Schmidt, R.P. and Turner, C.E. (2012) Hic-5 promotes invadopodia formation and invasion during TGF-β-induced epithelial-mesenchymal transition. J. Cell Biol. 197 421-437.
Deakin, N.O., Pignatelli, J., and Turner, C.E. (2012) Diverse roles for the Paxillin family of proteins in cancer. Genes and Cancer. 3 362-370.
Deakin, N.O. and Turner, C.E. (2014) Paxillin interacts with and inhibits HDAC6 in normal and malignant Cells to regulate microtubule acetylation, Golgi structural integrity and polarized migration J. Cell Biol. 206 395-413.