乳腺癌癌症干细胞是乳腺癌发生、发展、转移和治疗后复发的重要根源之一。申请人前期研究发现纤维鞘相互作用蛋白-FSIP1与乳腺癌转移、不良预后和化疗耐药显著相关。预实验显示：乳腺癌肿瘤干性因子SLUG可以调控乳腺癌干细胞的增殖和迁移；敲减SLUG后FSIP1表达下调；RNAseq和组织芯片数据显示FSIP1与Hippo通路有关。在此基础上，本研究拟以乳腺癌癌症干细胞模型/体外/小鼠体内模型，采用功能获得/缺失、Co-IP等技术探究：SLUG对FSIP1的调控作用及分子机制；SLUG-FSIP1信号激活Hippo通路的分子机制；SLUG/FSIP1/Hippo信号通路在乳腺癌干性维持中的作用及机制。通过揭示乳腺癌癌症干细胞中SLUG调控FSIP1表达的分子机制，阐明FSIP1/Hippo信号在肿瘤干细胞自我更新中的作用及机制，为以FSIP1为切入点靶向乳腺癌癌症干细胞提供实验依据。

Breast cancer stem cells are one of the important root cause of breast cancer occurrence, development, metastasis and recurrence after treatment. Our previous studies have found that Fibrous Sheath Interacting Protein 1-FSIP1 was significantly associated with breast cancer metastasis, poor prognosis, and chemotherapy resistance. Our recent experiments showed that stemness factor SLUG can regulate breast cancer stem cell proliferation and migration, SLUG knockdown can down-regulate FSIP1 expression, and RNAseq and tissue microarray data show that FSIP1 is related to the Hippo pathway. Based on this, this study intends to use breast cancer stem cells model/in vitro/mice in vivo model to explore: the regulatory effect of SLUG on FSIP1 and its molecular mechanism; Molecular mechanism of SLUG-FSIP1 signal activation of Hippo pathway; The role of SLUG/FSIP1/Hippo signaling pathway in stem maintenance of breast cancer combined by the gain or loss of functions, Co-IP and other technologies. By revealing the molecular mechanism of SLUG regulation of FSIP1 expression in breast cancer stem cells, elucidating the role and mechanism of FSIP1/Hippo signaling in cancer stem cell self-renewal, we will provide experimental evidence for targeting breast cancer stem cells with FSIP1 as the entry point.