Slit-Robo Signaling in Tumor Growth and Metastasis

肿瘤生长和转移中的 Slit-Robo 信号传导

基本信息

批准号：
8130391
负责人：
JIAN-GUO GENG
金额：
$ 31.18万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-12-01 至 2013-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8130391
关键词：
ABL1 gene Adenomatous Polyposis Coli Affinity Chromatography Attenuated Binding Carcinoma Cell membrane Cell surface Cells Chemotactic Factors Colon Carcinoma Complex Cues Data Diagnosis Diagnostic Down-Regulation Drosophila sli protein E-Cadherin Endothelial Cells Enzyme-Linked Immunosorbent Assay Epithelial Family Glycogen Synthase Kinases Growth Health Human Integral Membrane Protein Islets of Langerhans Laminin Receptor Large Intestine Carcinoma Leukocyte Chemotaxis Link Lymphangiogenesis Lymphatic Lymphatic Endothelial Cells Lymphatic Metastasis Malignant Neoplasms Malignant neoplasm of prostate Mediating Mesenchymal Mesentery Molecular Molecular Target Mus Neoplasm Metastasis Neurons Nuclear Oncogenes Pathogenesis Peptides Phosphorylation Play Primary Neoplasm Process Prognostic Marker Proteins Reporting Role Serum Signal Transduction Small Interfering RNA Staining method Stains TCF Transcription Factor Testing Therapeutic Tissues Transgenic Mice Tube Tumor Angiogenesis Tyrosine Vascular Endothelial Cell Xenograft Model adenoma angiogenesis autocrine axon guidance c-abl Proto-Oncogenes cancer cell cancer therapy carcinogenesis cell type design inhibitor/antagonist insulinoma knock-down lymph nodes melanoma migration mouse model neoplastic neutralizing monoclonal antibodies novel overexpression prognostic promoter receptor tool tumor tumor growth tumorigenesis

项目摘要

DESCRIPTION (provided by applicant): The Slit family of migratory cues is secreted by midline cells, endothelial cells and cancer cells. They bind to a family of cell-surface transmembrane proteins, Roundabout (Robo), and act as repellants for axon guidance and neuronal migration, endogenous inhibitors for leukocyte chemotaxis and chemoattractants for vascular endothelial cells. To assess the pathological significance and to elucidate the underlying molecular mechanisms for Slit-Robo signaling in the growth and metastasis of tumors, we will investigate (1) the effect of Slit-Robo signaling in lymphangiogenesis and lymphatic metastasis, the pathological role of Slit2 in tumor angiogenesis and growth and (2) the effect of Slit-Robo signaling on canonical Wnt signaling. We believe that these studies will not only deepen our understanding of the molecular mechanisms involved in tumor growth and metastasis, but also facilitate the use of Slit2 and Robo1 as the novel molecular targets for diagnosis and treatment of cancers. PUBLIC HEALTH RELEVANCE: Our study on Slit-Robo signaling in tumor growth and metastasis will not only deepen our understanding of the molecular mechanisms involved in tumor growth and metastasis, but also facilitate the use of Slit2 and Robo1 as the novel molecular targets of diagnosis and treatment of cancers.

描述（由申请人提供）：Slit家族的迁移线索由中线细胞、内皮细胞和癌细胞分泌。它们与细胞表面跨膜蛋白家族 Roundabout (Robo) 结合，并充当轴突导向和神经元迁移的排斥剂、白细胞趋化性的内源性抑制剂和血管内皮细胞的趋化剂。为了评估Slit-Robo信号在肿瘤生长和转移中的病理意义并阐明其潜在分子机制，我们将研究（1）Slit-Robo信号在淋巴管生成和淋巴转移中的作用，Slit2在肿瘤生长和转移中的病理作用。肿瘤血管生成和生长以及（2）Slit-Robo 信号传导对经典 Wnt 信号传导的影响。我们相信这些研究不仅将加深我们对肿瘤生长和转移的分子机制的理解，而且有助于利用Slit2和Robo1作为癌症诊断和治疗的新分子靶点。公共健康相关性：我们对肿瘤生长和转移中 Slit-Robo 信号传导的研究不仅将加深我们对肿瘤生长和转移分子机制的理解，而且有助于利用 Slit2 和 Robo1 作为诊断和转移的新分子靶点。癌症的治疗。