Functional Studies of Focal Adhesion Kinase

粘着斑激酶的功能研究

• 批准号: 6908986
• 负责人: Steven K. Hanks
• 金额: $ 30.2万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-12-01 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6908986
• 关键词: animal tissue; biological signal transduction; cell migration; cell transformation; colon neoplasms; enzyme activity; enzyme induction /repression; extracellular matrix; fibroblasts; focal adhesion kinase; gene mutation; genetic mapping; human tissue; integrins; laboratory mouse; metastasis; neoplasm /cancer invasiveness; phosphorylation; protein binding; protein protein interaction; protein structure function; protooncogene; site directed mutagenesis; tissue /cell culture; western blottings

DESCRIPTION (provided by applicant): Cancer mortality results in part from the development of variant tumor cells with a highly invasive and metastatic phenotype. The molecular events that contribute to the invasive/metastatic phenotype are poorly understood. Recent studies indicate that adhesion mediated signaling events involving a protein complex consisting of focal adhesion kinase (F AK), the Src protooncogene, and the Crk-associated substrate (CAS) function to regulate cell growth and migration. Other studies have linked these molecules to tumor invasion and metastasis. The broad long-term objective of the proposed studies is to determine if aberrant FAK-Src-CAS signaling contributes to the acquisition of the invasive/metastatic phenotype of human cancers. Toward this objective, the following three Specific Aims are planned: 1) Determine CAS protein-interaction motifs required for adhesion-regulated signaling, cell spreading, and migration; 2) Determine the role of GAS in Src-mediated cell transformation, invasion, and metastasis; and 3) Determine if enhanced signaling from the FA K-Src nexus can elevate the tumorigenic and metastatic potential of human colon carcinoma cell Iines. This work will help define the biological changes that underlie cancer spread and may lead to new preventive or treatment interventions.

描述(由申请人提供)：癌症死亡的部分原因是具有高度侵袭性和转移性表型的变异肿瘤细胞的发展。导致侵袭/转移表型的分子事件还知之甚少。最近的研究表明，黏附介导的信号事件涉及由粘着斑激酶(FAK)、原癌基因Src和Crk相关底物(CAS)组成的蛋白质复合体，具有调节细胞生长和迁移的功能。其他研究已经将这些分子与肿瘤的侵袭和转移联系起来。拟议研究的长期目标是确定异常的FAK-Src-CAS信号是否有助于获得人类癌症的侵袭/转移表型。为此，我们计划了以下三个具体目标：1)确定黏附调节信号、细胞扩散和迁移所需的CAS蛋白相互作用基序；2)确定GAS在Src介导的细胞转化、侵袭和转移中的作用；以及3)确定来自FA K-Src网络的增强信号是否可以提高人结肠癌细胞系的致瘤和转移潜能。这项工作将有助于确定癌症传播背后的生物学变化，并可能导致新的预防或治疗干预措施。