肿瘤干细胞被认为与脑转移关系密切。申请者从乳腺癌组织中建立了可长期体外培养的乳腺癌干细胞（BCSC）系（专利申请号201510330647.5），证实POMC（阿片促黑素细胞皮质素原）是维持BCSC特性的关键分子（Int J Cancer 2017）。已报道，SOX2与BCSC相关。申请者通过基因芯片及验证分析发现POMC和SOX2在乳腺癌脑转移组织中高表达并呈正相关。因此，申请者提出POMC可能通过上调SOX2表达，增强乳腺癌干性和脑转移。本项目拟采用CRISPR/Cas9、体外血脑屏障模型和活体动物成像等技术，明确POMC通过上调SOX2表达，增强BCSC的干性，促进BCSC在脑组织中定植和生长；探讨POMC调控乳腺癌脑转移的分子机制及临床相关性。本项目的实施将初步阐明POMC增强乳腺癌干性和脑转移的作用机制，为乳腺癌脑转移的发生发展、预后判断及精准靶向治疗提供理论基础和临床应用依据。

Cancer stem cells are thought to be closely related to brain metastases. The applicant has established two breast cancer stem cell (BCSC) lines that can be cultured in vitro for long periods from breast cancer tissues (Patent Application No. 201510330647.5), confirming that POMC (pro-opiomelanocortin) is a key molecule that maintains BCSC properties (Int J Cancer 2017). It has been reported that SOX2 is associated with BCSC. Through gene chips and validation analysis, the applicant found that POMC and SOX2 were highly expressed in brain metastases of breast cancer, and their expression was positively correlated. Therefore, the applicant hypothesized that POMC may enhance breast cancer stemness and brain metastasis by up-regulating SOX2 expression. This project intends to use CRISPR / Cas9, in vitro blood-brain barrier model and in vivo animal imaging technology to confirm that POMC enhances the stemness of BCSC and promotes BCSC colonization and growth in brain tissue by up-regulating SOX2 expression, and to explore the molecular mechanism and clinical relevance of POMC in regulating brain metastases of breast cancer. The implementation of this project will initially clarify the role of POMC in enhancing breast cancer stemness and brain metastasis and provide theoretical basis and clinical application basis for the occurrence, development, prognosis and accurate targeted therapy of breast cancer brain metastasis.