Junctions, Cytoskeleton and Matrix of the Oral Epithelium-Project 3

DESCRIPTION: (provided by the applicant) Approximately90 percent of oral cancers are squamous cell carcinomas originating from theoral epithelium. It is the sixth most prevalent solid tumor worldwide. Thedevelopment and progression of oral cancer involves alterations in cell-celljunctions, cell-matrix adhesion sites and their associated cytoskeletonelements. The molecular bases of these alterations has been and continues to bethe focus of this program project. The overall goal of the fourprojects andcores is to gain new insight into how the extracellular matrix influences cellbehavior, how the functions of extracellular matrix elements are modifiedpost-translationally by specific proteolytic events, how cytoskeleton changesimpact cell motility and organization and how intercellular junctionassembly/disassembly is regulated in normal and tumor epithelial cells. Thisproposal details the continuation of a concentrated and multidisciplinary setof studies by an interactive team of investigators at Northwestern UniversityMedical School. The four component projects are highly interdependent. Thesubproject, "Laminin-5 and hemidesmosomes in oral epithelial cells" will study themolecular mechanisms underpinning the way matrix impacts cell adhesion andmotility of oral cancer cells via the activity of their cell surfacecomponents. The subproject, "Cell adhesion and proteolytic potential in oralsquamous cell carcinoma" will focus on the molecular mechanisms regulatingmetastasis-associated proteinases and the structural consequences of matrixdegradation by cancer cells.The subproject, "Cytoskeletal-cell surface interactionin oral epithelial cells" will test the hypothesis that changes in expressionof intermediate filament proteins regulates cell migration and tumor cellmetastasis. The subproject, "Regulation of cell-cell junction structure and dynamicsin oral tumor cell migration" will investigate the role of reversiblemodulation in cadherin-based cell-cell adhesion in oral cell