Slit Signaling in Breast Cancer

描述（由申请人提供）：我们的长期目标是了解肿瘤发生和转移的分子机制。本应用程序主要研究乳腺癌中的狭缝信号。狭缝基因家族编码引导神经元迁移和抑制趋化因子激活的分泌蛋白。Slit是第一个被报道的由细胞产生的趋化因子抑制剂。观察到Slit在一系列肿瘤中经常失活，这表明Slit基因在肿瘤抑制中起作用。我们已经建立了几个实验，并表明Slit在体外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，Slit在体内抑制肿瘤转移。我们的假设得到了初步结果的支持，即Slit信号传导对抑制癌症转移很重要。我们计划研究Slit信号在乳腺癌侵袭中的作用。以及体内和体外的转移。我们将剖析肿瘤细胞中参与Slit功能的信号转导途径。我们建立了分析方法并制备了试剂来研究裂缝信号通路如何与趋化因子信号转导通路进行通信。这些研究将为研究肿瘤侵袭转移机制提供新的思路。增强或激活限制或抑制癌症侵袭/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.