HGF/MET AND ADHESION RECEPTORS IN ORAL CANCER

口腔癌中的 HGF/MET 和粘附受体

• 批准号: 6379779
• 负责人: RANDALL H KRAMER
• 金额: $ 26.19万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-04-01 至 2003-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6379779
• 关键词: athymic mouse; biological signal transduction; blocking antibody; cadherins; cell adhesion; cell growth regulation; cell migration; cell motility; cellular oncology; flow cytometry; growth factor receptors; hepatocyte growth factor; integrins; intercellular connection; molecular oncology; monoclonal antibody; neoplasm /cancer invasiveness; oral pharyngeal neoplasm; phosphorylation; protein structure function; receptor binding; receptor expression; squamous cell carcinoma; tissue /cell culture; western blottings

DESCRIPTION (Adapted from investigator's Abstract): Squamous cell carcinoma (SCC) of the oral cavity spreads by local extension and by lymphatic metastasis. Tumor invasion requires cell locomotion, which in turn requires motility factors. One such factor is hepatocyte growth factor (HGF), a strong stimulator of cell motility and invasion in oral SCC cells. The binding of HGF to its receptor, Met, triggers downstream signaling events that induce disruption of intercellular cadherin junctions, activate integrin-ECM binding, mobilizes the associated cytoskeleton, and finally initiates cell movement. The overall goal of the proposed studies is to understand, at the molecular and cellular levels, how HGF/Met governs the motile and invasive response of oral SCC cells. The hypothesis to be addressed is that the invasive response elicited by HGF via Met is regulated through cadherin- and integrin-mediated adhesion. The aims are: 1) to analyze how intercellular adhesion contacts modulate HGF-induced motility; 2) to define the mechanisms that regulate HGF-mediated dispersion of multicellular colonies; and 3) to determine whether HGF receptor and integrin receptors have synergistic roles in disrupting cadherin/catenin function during HGF-induced cell motility.

描述（根据研究者的摘要改编）：鳞状细胞癌 口腔的（SCC）通过局部延伸和淋巴扩散 转移。 肿瘤侵袭需要细胞运动，这又需要 运动因素。 这样的因素之一是肝细胞生长因子（HGF），A 细胞运动和口服SCC细胞浸润的强刺激剂。 这 HGF与其受体的结合，Met，触发下游信号事件 引起细胞间钙粘蛋白连接的破坏，激活 整联蛋白-ECM结合，动员相关的细胞骨架，最后 启动细胞运动。 拟议研究的总体目标是 在分子和细胞水平上了解HGF/MET如何控制 口服SCC细胞的运动和侵入性反应。 假设是 解决的是，HGF通过MET引起的侵入性响应受到调节 通过钙粘蛋白和整联蛋白介导的粘附。 目的是：1） 分析细胞间粘附接触如何调节HGF诱导的运动性； 2）定义调节HGF介导的分散体的机制 多细胞菌落； 3）确定HGF受体和是否是否 整联蛋白受体在破坏钙粘蛋白/catenin中具有协同作用 HGF诱导的细胞运动过程中的功能。