Mechanism Of Extracellular Matrix Protein (ECM1) Promoting Metastasis Of Epithelial Ovarian Cancer

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 activation of NF-κB can promote the transcription of the extracellular matrix protein 1(ECM1), 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 activation of NF-κB promotes ECM1 transcription, and the regulation model that ECM1 interacts with αXβ2 to activate Slug/Snail. The results show the mechanism that ECM1 promotes invasion and metastasis of epithelial ovarian cancer through the NF-κB/ECM1/αXβ2/ Slug, Snail signal axis, and the association between the signal axis and the clinical pathological characteristics of epithelial ovarian cancer patients including survival and prognosis, which may explore the novel molecular targets for precise and effective treatment of epithelial ovarian cancer.