Slit Signaling in Breast Cancer

描述(由申请者提供)：我们的长期目标是了解肿瘤发生和转移的分子机制。本应用侧重于研究乳腺癌中的缝隙信号。Sit基因家族编码分泌的蛋白质，引导神经元迁移并抑制趋化因子的激活。Sit是第一个报道的由细胞产生的趋化因子抑制剂。Sit基因在一系列肿瘤中经常失活的观察结果表明，Sit基因在肿瘤抑制中发挥了作用。我们已经建立了几种检测方法，并表明Sit在体外可以抑制趋化因子诱导的乳腺癌细胞的侵袭和迁移。我们的初步研究表明，Sit可以抑制体内的癌症转移。我们的假设得到了初步结果的支持，即SILT信号对于抑制癌症转移是重要的。我们计划在体外和体内研究SILT信号在乳腺癌侵袭和转移中的作用。我们将剖析参与癌细胞缝隙功能的信号转导通路。我们已经建立了检测方法，并准备了试剂来研究Sit-信号通路与趋化因子信号转导通路的联系。所提出的研究将为控制肿瘤侵袭和转移的机制提供新的见解。增强或激活限制或抑制肿瘤侵袭/转移的内源性机制可能为治疗转移性疾病提供新的途径。

DESCRIPTION (provided by applicant): Our long-term goal is to understand the molecular mechanisms underlying tumor development and metastasis. This application focuses on studying Slit signaling in breast cancer. Slit gene family encodes secreted proteins guiding neuronal migration and inhibiting chemokine activation. Slit is the first reported chemokine inhibitor produced by cells. The observation that Slit is frequently inactivated in a range of tumors indicates a role of Slit gene in tumor suppression. We have established several assays and shown that Slit inhibits chemokine-induced invasion and migration of breast cancer cells in vitro. Our preliminary study suggests that Slit suppresses cancer metastasis in vivo. Our hypothesis, supported by the preliminary results, is that Slit signaling is important for inhibiting cancer metastasis. We plan to examine the role of Slit signaling in breast cancer invasion .and metastasis in vitro and in vivo. We will dissect the signal transduction pathways involved in Slit function in cancer cells. We have established assays and prepared reagents to investigate how Slit-signaling pathway communicates with chemokine signal transduction pathways. The proposed studies will provide new insights into mechanisms controlling tumor invasion and metastasis. Enhancing or activating the endogenous mechanisms that restrict or suppress cancer invasion/metastasis may likely provide novel approaches for treating metastatic diseases.