ROLE OF CORTACTIN IN HEAD AND NECK CANCER

Cortactin 在头颈癌中的作用

• 批准号: 8167957
• 负责人: Scott A Weed
• 金额: $ 21.91万
• 依托单位: WEST VIRGINIA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8167957
• 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; 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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。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。列出的机构是 对于中心，这不一定是调查员的机构。 皮质素是一种皮质肌动蛋白结合蛋白和底物，用于各种肿瘤致癌激酶。 Cortactin与肌动蛋白相关（ARP）2/3蛋白复合物相互作用，该蛋白复合物通过在Motile细胞的前缘启动和维持肌动蛋白丝的聚合来驱动细胞运动。 Cortactin在几种人类癌症中过表达，由于染色体11Q11Q13的扩增，最常见于头和颈部鳞状细胞癌（HNSCC）。 HNSCC是折磨口腔和相关组织的最常见癌症，并遵循明确定义的从增生到癌的发展范围。我们实验室的最新工作表明，Cortactin的过表达直接通过增强ARP2/3复合物的激活以及通过SRC家庭激酶介导的酪氨酸磷酸化来直接调节HNSCC的运动和侵袭。 这些研究表明，皮质素的过表达在HNSCC侵袭和转移中起着直接的作用。 然而，在HNSCC中，Cortactin过表达过表达的精确阶段，Cortactin作为HNSCC入侵的预后标志物的适合性，Cortactin Molecules cortactin与Cortactin与Cortactin过表达在HNSCC进展中的影响尚未得到研究。 该提案将通过三个目的解决这些问题：AIM 1将在HNSCC进展过程中确定阶段，其中cortactin基因座被放大，蛋白质过表达/磷酸化在酪氨酸和丝氨酸残基上。 AIM 2将通过蛋白质组学方法鉴定HNSCC细胞中与Cortactin相互作用的蛋白质+/-染色体11q13扩增。 AIM 3将在口腔癌中开发一种Cortactin的转基因小鼠模型，以评估Cortactin如何影响HNSCC的发育和进展。