Junctions, Cytoskeleton & Matrix of the Oral Epithelium

描述：（由申请人提供）大约 90%的口腔癌是鳞状细胞癌， 口腔上皮它是全球第六大最常见的实体瘤。的 口腔癌的发生和发展涉及细胞-细胞 连接、细胞-基质粘附位点及其相关的细胞骨架 元素这些改变的分子基础已经并将继续是 这个项目的重点。四项工程的总体目标和 核心是获得细胞外基质如何影响细胞的新见解， 行为，细胞外基质元素的功能如何被修改 通过特定的蛋白水解事件，细胞骨架如何变化， 影响细胞运动和组织以及细胞间连接 在正常和肿瘤上皮细胞中调节组装/拆卸。这 提案详细说明了集中和多学科的延续 西北大学的一个互动研究小组 医学院这四个组成部分项目相互依存程度很高。的 子项目“口腔上皮细胞中的层粘连蛋白-5和半桥粒”将研究 基质影响细胞粘附的分子机制， 口腔癌细胞通过其细胞表面活性的运动性 件.该子项目，“口腔中的细胞粘附和蛋白水解潜力 鳞状细胞癌”将集中在分子机制调节 转移相关蛋白酶和基质的结构后果 该子项目，“细胞间隙-细胞表面相互作用 ”将检验口腔上皮细胞表达变化的假设， 调节细胞迁移和肿瘤细胞 转移子项目“细胞-细胞连接结构和动力学的调节 在口腔肿瘤细胞迁移中的作用”将研究可逆的 调节口腔细胞迁移中基于钙粘蛋白的细胞-细胞粘附， 发生在肿瘤进展过程中。这些多学科研究将提供 关于癌细胞在这场毁灭性的疾病中传播的精确信息， 癌

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.