The role of deubiquitinating enzyme USP33 in Slit-Robo signaling in lung cancer

去泛素化酶 USP33 在肺癌 Slit-Robo 信号传导中的作用

• 批准号: 8632559
• 负责人: JANE Y WU
• 金额: $ 45.67万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-03-07 至 2019-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8632559
• 关键词: Affect; Alpha 1 Casein Kinase 1; Animal Genetics; Animal Model; Biochemical; Biological; Biological Assay; Cancer Control; Cancer Patient; Cell Death; Cell Proliferation; Cells; Data; Deubiquitinating Enzyme; Development; Disease; Drosophila sli protein; Enzymes; GTPase-Activating Proteins; Gene Targeting; Genes; Genetic; Genetic Variation; Goals; Human; Human Development; In Vitro; Lead; Ligands; Lung Neoplasms; Malignant Neoplasms; Malignant neoplasm of lung; Mediating; Methods; Methylation; Microscopy; Molecular; Mutate; Mutation; Neoplasm Metastasis; Neurons; Pathway interactions; Patients; Play; Publishing; Research; Role; Sampling; Sequence Analysis; Signal Pathway; Signal Transduction; Signal Transduction Pathway; Signaling Molecule; TP53 gene; Testing; Time; Tumor Suppression; Tumor Suppressor Genes; Tumor Suppressor Proteins; Work; angiogenesis; cancer cell; cancer type; cell motility; chemokine; deep sequencing; design; enzyme activity; extracellular; in vitro Assay; in vivo; lung tumorigenesis; migration; mutant; neuronal guidance; new therapeutic target; novel; outcome forecast; protein function; public health relevance; receptor; research study; tumor; tumorigenesis; wound

Our long-term goal is to understand molecular mechanisms underlying novel tumor suppressor genes Slit and USP33. Our previous work and preliminary data suggest that a prototypical neuronal repellent, Slit, is an important tumor suppressor for lung cancer and that Slit expression predicts better prognosis in lung cancer patients. To dissect Slit signaling pathways and examine mechanisms underlying tumor suppression in lung cancer, we examined how signal-transducing molecules interacted with Slit receptor Roundabout (Robo). We identified the deubiquitinating enzyme, USP33, as a critical component in Slit-Robo signaling pathway(s) in lung cancer. This proposal aims to examine Slit-Robo-USP33 mediated tumor suppression in lung cancer using molecular, biochemical and cell biological methods in combination with animal models and sequence analyses of human lung cancer samples. Our pilot deep-sequencing studies support the tumor suppressive function of Slit-Robo- USP33 pathway and the involvement of the downstream signaling molecules. We have established both in vitro assays and animal models to study the role of this newly uncovered tumor suppression pathway in lung cancer development. We plan to use these integrated molecular, cellular and genetic approaches to define the role of Slit-Robo signaling in suppressing lung cancer. Our proposed work will help elucidate molecular mechanisms underlying Slit and USP33 tumor suppressors and determine the role of genetic variations in Slit or USP33 and their downstream genes in development of human lung cancer.

我们的长期目标是了解新型肿瘤抑制基因Slit和Slit的分子机制