Slit-Robo Signaling in Tumor Growth and Metastasis

描述(申请人提供)：SILT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，作为轴突引导和神经元迁移的排斥剂、白细胞趋化的内源性抑制物和血管内皮细胞的趋化剂。为了评价Sit-Robo信号在肿瘤生长和转移中的病理意义并阐明其潜在的分子机制，我们将研究(1)Sit-Robo信号在淋巴管生成和淋巴转移中的作用，Slit2在肿瘤血管生成和生长中的病理作用以及(2)Sit-Robo信号对规范的Wnt信号的影响。我们相信，这些研究不仅将加深我们对参与肿瘤生长和转移的分子机制的理解，而且有助于将Slit2和Robo1作为新的分子靶点用于癌症的诊断和治疗。公共卫生意义：我们对Sit-Robo信号在肿瘤生长和转移中的研究不仅将加深我们对参与肿瘤生长和转移的分子机制的理解，而且有助于将Slit2和Robo1作为新的分子靶点用于癌症的诊断和治疗。

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.