HGF/MET AND ADHESION RECEPTORS IN ORAL CANCER

口腔癌中的 HGF/MET 和粘附受体

• 批准号: 6176065
• 负责人: RANDALL H KRAMER
• 金额: $ 25.56万
• 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/6176065
• 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（改编自研究者的摘要）：鳞状细胞癌 口腔鳞状细胞癌（SCC）通过局部扩展和淋巴管扩散 转移。 肿瘤侵袭需要细胞运动，而细胞运动又需要 动力因素。 其中一个因子是肝细胞生长因子 (HGF)，它是一种 口腔鳞状细胞癌细胞运动和侵袭的强刺激剂。 这 HGF 与其受体 Met 结合，触发下游信号事件 诱导细胞间钙粘蛋白连接破坏，激活 整合素-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 口腔鳞状细胞癌细胞的运动和侵袭反应。 假设为 所解决的问题是 HGF 通过 Met 引起的侵入反应受到调节 通过钙粘蛋白和整合素介导的粘附。 目标是：1） 分析细胞间粘附接触如何调节 HGF 诱导的运动； 2）定义调节HGF介导的分散的机制 多细胞集落； 3) 确定HGF受体和 整合素受体在破坏钙粘蛋白/连环蛋白方面具有协同作用 HGF 诱导的细胞运动期间的功能。