ROLE OF CORTACTIN IN HEAD AND NECK CANCER

Cortactin 在头颈癌中的作用

• 批准号: 7960377
• 负责人: Scott A Weed
• 金额: $ 24.32万
• 依托单位: WEST VIRGINIA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7960377
• 关键词: 11q13; Actin-Binding Protein; Actins; Address; Carcinoma; Cells; Chromosomes; Complex; Computer Retrieval of Information on Scientific Projects Database; Development; Funding; Grant; Head and Neck Cancer; Head and Neck Squamous Cell Carcinoma; Human; Hyperplasia; Institution; Laboratories; Malignant Epithelial Cell; Malignant Neoplasms; Mediating; Methods; Microfilaments; Neoplasm Metastasis; Oncogenic; Oral cavity; Phosphotransferases; Play; Prognostic Marker; Proteins; Proteomics; Research; Research Personnel; Resources; Role; Serine; Signal Transduction; Source; Staging; Tissues; Transgenic Mice; Tyrosine; Tyrosine Phosphorylation; United States National Institutes of Health; Work; cell motility; human EMS1 protein; malignant mouth neoplasm; mouse model; overexpression; polymerization; protein complex; src-Family Kinases; tumor

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. Cortactin is a cortical actin-binding protein and substrate for various tumor-promoting oncogenic kinases. Cortactin interacts with the actin-related (Arp) 2/3 protein complex, which drives cell motility by initiating and maintaining polymerization of actin filaments at the leading edge of motile cells. Cortactin is overexpressed in several human cancers, most frequently in head and neck squamous cell carcinoma (HNSCC) as a result of amplification of chromosome 11q13. HNSCC is the most common cancer that afflicts the oral cavity and associated tissues, and follows a well-defined paradigm of progression from hyperplasia to carcinoma. Recent work from our laboratory has demonstrated that cortactin overexpression directly modulates HNSCC motility and invasion by enhanced activation of Arp2/3 complex and by tyrosine phosphorylation mediated by Src-family kinases. These studies suggest that cortactin overexpression plays a direct role in HNSCC invasion and metastasis. However, the precise stage in HNSCC that cortactin is overexpressed, the suitability of cortactin as a prognostic marker for HNSCC invasion, the molecules cortactin associates with and the influence of cortactin overexpression in HNSCC progression have not been investigated. This proposal will address these questions through three aims: Aim 1 will determinine the stage(s) during HNSCC progression in which the cortactin locus is amplified, and the protein overexpressed/phosphorylated on tyrosine and serine residues. Aim 2 will identify proteins that interact with cortactin in HNSCC cells +/- chromosome 11q13 amplification by proteomic methods. Aim 3 will develop a transgenic mouse model of cortactin in oral cancer to evaluate how cortactin influences HNSCC development and progression.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 Cortactin 是一种皮质肌动蛋白结合蛋白，也是各种促肿瘤致癌激酶的底物。 Cortactin 与肌动蛋白相关 (Arp) 2/3 蛋白复合物相互作用，后者通过启动和维持运动细胞前缘肌动蛋白丝的聚合来驱动细胞运动。 Cortactin 在多种人类癌症中过度表达，最常见的是由于染色体 11q13 扩增而导致的头颈鳞状细胞癌 (HNSCC)。 HNSCC 是影响口腔和相关组织的最常见癌症，并遵循从增生到癌的明确发展模式。我们实验室最近的工作表明，cortactin 过度表达通过增强 Arp2/3 复合物的激活和 Src 家族激酶介导的酪氨酸磷酸化直接调节 HNSCC 的运动和侵袭。 这些研究表明 cortactin 过度表达在 HNSCC 侵袭和转移中发挥直接作用。 然而，cortactin 在 HNSCC 中过度表达的精确阶段、cortactin 作为 HNSCC 侵袭预后标志物的适用性、cortactin 相关分子以及 cortactin 过度表达对 HNSCC 进展的影响尚未得到研究。 该提案将通过三个目标解决这些问题：目标 1 将确定 HNSCC 进展过程中皮质蛋白基因座扩增的阶段，以及酪氨酸和丝氨酸残基上蛋白质过度表达/磷酸化的阶段。 目标 2 将通过蛋白质组学方法鉴定与 HNSCC 细胞 +/- 染色体 11q13 扩增中的皮质蛋白相互作用的蛋白质。目标 3 将开发口腔癌 Cortactin 转基因小鼠模型，以评估 Cortactin 如何影响 HNSCC 的发生和进展。