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.

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