强转移性是上皮卵巢癌致死率极高的主要原因之一，因此，搞清其转移机制是有效治疗此类卵巢癌的首要任务。最近的研究发现，极光激酶A(Aur A)对肿瘤转移及其重要。我们的前期研究提示Aur A可能通过激活NF-κB促进细胞外基质蛋白-1（ECM1)的转录；而ECM1可能与整合素αXβ2互作，活化ZEB1并诱导上皮卵巢癌细胞的上皮-间质转化（EMT）和肿瘤的侵袭及转移。本研究拟通过基因过表达或沉默、药物处理、蛋白-蛋白或蛋白-DNA互作、基因突变等方法，从分子、细胞、动物和人体标本水平分别研究Aur A激活NF-κB的信号途径；NF-κB启动ECM1转录的方式；ECM1与αXβ2互作及活化ZEB1的模式，基本阐明Aur A通过NF-κB/ECM1/αXβ2/ZEB1信号轴促进上皮卵巢癌侵袭和转移的机制，及其与上皮卵巢癌患者生存和预后等临床病理学特征的相关性，以期探寻精准治疗上皮卵巢癌的新型分子靶标

Strong metastasis is one of the major reasons for high mortality of epithelial ovarian cancer. Thus, understanding of the metastatic mechanism is the priority to treat the disease. Recent studies have revealed that Aurora kinase A (Aur A) plays an important role in cancer metastasis. Our preliminary work has suggested that Aur A may promote the transcription of the extracellular matrix protein 1 (ECM1) through activation of NF-κB, and that the interaction of ECM1 with integrin αXβ2 may activate ZEB1 to induce Epithelial-Mesenchymal Transition (EMT), invasion, and metastasis of epithelial ovarian cancer cells. This proposal is designed, by using the methods such as gene overexpression or silencing, drug treatment, protein-protein or protein-DNA interactions, gene mutagenesis, and so on, and at levels of molecules, cells, animals, and human specimens, respectively, to study the signaling pathway that Aurora A activates NF-κB, the detailed style that NF-κB promotes ECM1 transcription, and the regulation model that ECM1 interacts with αXβ2 to activate ZEB1, which may uncover the mechanism that Aurora A promotes invasion and metastasis of epithelial ovarian cancer through the NF-κB/ECM1/αXβ2/ZEB1 signal axis, and the association between the signal axis and the clinical pathological characteristics of epithelical ovarian cancer patients including survival and prognosis, which may explore the novel molecular targets for precise and effective treatment of epithelial ovarian cancer