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Syk and associated proteins in breast cancer

乳腺癌中的 Syk 和相关蛋白

基本信息

批准号：
7613604
负责人：
ROBERT L GEAHLEN
金额：
$ 3.61万
依托单位：
PURDUE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-12-06 至 2010-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7613604
关键词：
Antigens Arts Benign Binding Biochemical Genetics Breast Breast Cancer Cell Carcinoma Cell Adhesion Cell Communication Cell Death Cell Survival Cell physiology Cell-Cell Adhesion Cells Critical Pathways Development Disruption Enzymes Epigenetic Process Epithelial Cells Epithelium Evaluation Extracellular Matrix Genetic Growth Health Immune response Immune system Invasive Light Malignant - descriptor Measures Mediating Methodology Microscopic Neoplasm Metastasis Oncogene Activation Oncogene Proteins Oncogenes Pathway interactions Personal Satisfaction Phenotype Phosphotyrosine Play Predisposition Process Property Protein Tyrosine Kinase Proteins Proteome Regulation Research Role Signal Pathway Signal Transduction Therapeutic Thinking Tumor Necrosis Factor-alpha Tumor Necrosis Factors Tumor Suppressor Proteins Tumor-Suppressor Gene Inactivation United States Woman base cancer cell cell growth cell motility human TNF protein malignant breast neoplasm malignant phenotype neoplastic cell novel novel therapeutics protein function protein protein interaction response src Homology Region 2 Domain therapeutic target transcription factor tumor progression tumorigenesis tumorigenic

项目摘要

In breast cancer, tumorigenesis occurs through an accumulation of genetic and epigenetic changes in epithelial cells involving both the activation of oncogenes and the inactivation of tumor suppressor genes. The Syk protein-tyrosine kinase, known best for its roles in the immune system, has recently been identified as a tumor suppressor in breast cancer; its expression being inversely correlated with malignant cell growth and metastasis. This is an unusual property for a tyrosine kinase, enzymes more typically found as the products of oncogenes. Thus, an understanding of how Syk functions to suppress the malignant phenotype of breast cancer cells is of considerable importance to our understanding of the critical pathways involved in growth control in breast epithelial cells and to the identification of possible, novel therapeutic targets. Preliminary studies have led to the hypothesis that Syk regulates two important aspects of of epithelial cell function: 1) cellular responses to tumor necrosis factor (TNF), a factor that regulates cell death/cell survival decisions and 2) cell adhesion and motility. These hypotheses are based on the identification of Syk- interacting proteins that participate in each of these pathways. The research proposed in this project will 1) characterize the physical and functional interactions between Syk and components of the TNF-signaling pathway with an emphasis on the characterization of a novel Syk-interacting protein thought to participate in this pathway; 2) characterize the critical structural features and mechanisms by which Syk, through its interacting partners, regulates cell adhesion and motility; and 3) characterize through phosphoproteomics studies the substrates and binding partners important for Syk's regulatory functions in breast epithelial cells. Methodologies to be employed include 1) genetic, biochemical and microscopic evaluations of protein- protein interactions and the consequences of their disruption and 2) state-of-the-art analyses of the phosphoproteome of Syk-expressing cells.

在乳腺癌中，肿瘤发生是通过遗传和表观遗传变化的积累发生的