Slit-Robo Signaling in Tumor Growth and Metastasis

肿瘤生长和转移中的 Slit-Robo 信号传导

• 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
• 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

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家族的迁移信号由中线细胞、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，并作为轴突引导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信号传导在肿瘤生长和转移中的病理学意义并阐明其潜在的分子机制，我们将研究（1）Slit-Robo信号传导在淋巴管生成和淋巴转移中的作用，Slit 2在肿瘤血管生成和生长中的病理学作用和（2）Slit-Robo信号传导对经典Wnt信号传导的作用。 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，而且将促进Slit 2和Robo 1作为诊断和治疗癌症的新分子靶点。 公共卫生相关性：研究Slit-Robo信号通路在肿瘤生长和转移中的作用，不仅可以加深我们对肿瘤生长和转移分子机制的认识，而且有助于将Slit 2和Robo 1作为肿瘤诊断和治疗的新分子靶点。