Junctions, Cytoskeleton & Matrix of the Oral Epithelium

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DESCRIPTION: (provided by the applicant) Approximately 90 percent of oral cancers are squamous cell carcinomas originating from the oral epithelium. It is the sixth most prevalent solid tumor worldwide. The development and progression of oral cancer involves alterations in cell-cell junctions, cell-matrix adhesion sites and their associated cytoskeleton elements. The molecular bases of these alterations has been and continues to be the focus of this program project. The overall goal of the fourprojects and cores is to gain new insight into how the extracellular matrix influences cell behavior, how the functions of extracellular matrix elements are modified post-translationally by specific proteolytic events, how cytoskeleton changes impact cell motility and organization and how intercellular junction assembly/disassembly is regulated in normal and tumor epithelial cells. This proposal details the continuation of a concentrated and multidisciplinary set of studies by an interactive team of investigators at Northwestern University Medical School. The four component projects are highly interdependent. The subproject, "Laminin-5 and hemidesmosomes in oral epithelial cells" will study the molecular mechanisms underpinning the way matrix impacts cell adhesion and motility of oral cancer cells via the activity of their cell surface components. The subproject, "Cell adhesion and proteolytic potential in oral squamous cell carcinoma" will focus on the molecular mechanisms regulating metastasis-associated proteinases and the structural consequences of matrix degradation by cancer cells.The subproject, "Cytoskeletal-cell surface interaction in oral epithelial cells" will test the hypothesis that changes in expression of intermediate filament proteins regulates cell migration and tumor cell metastasis. The subproject, "Regulation of cell-cell junction structure and dynamics in oral tumor cell migration" will investigate the role of reversible modulation in cadherin-based cell-cell adhesion in oral cell migration that occurs during tumor progression. These multidisciplinary studies will provide precise information about the dissemination of cancer cells in this devastating cancer.