COBRE: UNE MED CTR: P1: ROLE OF DESMOSOMES IN ORAL SQUAMOUS CELL CARCINOMA

COBRE：UNE MED CTR：P1：桥粒在口腔鳞状细胞癌中的作用

• 批准号: 7382053
• 负责人: JAMES K WAHL
• 金额: $ 26.74万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7382053
• 关键词: COBRE; UNE; MED; CTR; P1

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Desmosomes are prominent cell-cell junctions in stratified squamous epithelial tissues, whose composition varies among cells of the different layers of the tissue. It is not known why cells utilize different components to assemble desmosomes within the same tissue. However, it is likely that desmosomes comprised of different molecular components perform diverse functions and lead to altered adhesive characteristics. Desmosomal protein expression is generally reduced in squamous cell carcinomas; however, the contribution of these proteins to tumorigenesis is largely unknown. Our long-term goals are to understand the role desmosomes play in maintaining the normal phenotype of squamous epithelial tissues and to determine if their alteration during tumorigenesis influences cellular behavior. Our hypothesis is that changes in desmosomal composition result in differential adhesion and/or altered cell-cell signaling. Our laboratory has extensive experience in functional analysis of cell-cell adhesion and cell motility, and we are positioned to make significant contributions to our understanding of desmosome function and the role this cellular structure plays in the development of squamous cell carcinomas. The specific aims are: 1) To determine if the composition of desmosomes influences cell adhesion, proliferation and motility; and 2) To further understand the function of plakophilin-1 in the desmosome and in the nucleus. Plakophilin-1 is a desmosomal protein that is found in the nucleus as well as in the plasma membrane, which led us to propose that plakophilin-1 participates in nuclear signaling that may be linked to desmosomal adhesion. We will use structure/function studies to investigate the mechanism of nucleo-cytoplasmic transport of plakophilin-1 ; use a unique "activatible" form of plakophilin-1 to investigate the role of this protein in adhesion and in cellular signaling; and investigate nuclear proteins that associate with plakophilin-l. Collectively, the studies proposed herein will define the contribution of desmosomal components to cellular motility, invasiveness and signaling.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子弹和调查员（PI）可能已经从其他NIH来源获得了主要资金，因此可以在其他清晰的条目中代表。列出的机构适用于该中心，这不一定是调查员的机构。脱骨小体是分层鳞状上皮组织中突出的细胞 - 细胞连接，其组成在组织的不同层的细胞之间变化。尚不清楚为什么细胞利用不同的成分在同一组织中组装脱骨体。但是，由不同分子成分组成的脱染色体可能执行不同的功能，并导致粘附特性改变。在鳞状细胞癌中，脱骨蛋白表达通常会降低。但是，这些蛋白质对肿瘤发生的贡献在很大程度上尚不清楚。我们的长期目标是了解脱糖体在维持鳞状上皮组织的正常表型中的作用，并确定其在肿瘤发生过程中的改变是否会影响细胞行为。我们的假设是脱骨组成的变化会导致差异粘附和/或细胞细胞信号改变。我们的实验室在细胞 - 细胞粘附和细胞运动性的功能分析方面具有丰富的经验，我们有能力为我们对向肌功能的理解做出重大贡献，并且该细胞结构在鳞状细胞癌的发展中起着作用。具体目的是：1）确定脱糖体的组成是否影响细胞粘附，增殖和运动； 2）进一步了解plakophilin-1在朝下和核中的功能。 plakophilin-1是一种在细胞核和质膜中发现的脱发蛋白，这使我们提出plakophilin-1参与可能与脱骨粘附有关的核信号传导。我们将使用结构/功能研究来研究plakophilin-1的核总质转运的机理；使用plakophilin-1的独特的“可活动性”形式研究该蛋白在粘附和细胞信号中的作用；并研究与plakophin-L相关的核蛋白。总的来说，本文提出的研究将定义脱骨成分对细胞运动，侵入性和信号传导的贡献。