基于微流控芯片探讨膜蛋白LDLR调控乳腺癌干细胞转移潜能的机制研究

乳腺癌干细胞（BCSC）在乳腺癌转移过程中发挥重要作用。本项目前期通过高通量组学筛选出脂代谢通路在BCSC中显著富集，且膜蛋白LDLR在BCSC中特异性高表达、与乳腺癌不良预后密切相关，但LDLR发挥促BCSC转移的功能及其机制尚不清楚。我们推测，膜蛋白LDLR通过脂代谢途径促进乳腺癌干细胞转移。本项目拟利用微流控芯片技术探讨LDLR调控BCSC转移的作用及其分子机制。具体如下：（1）在优化的微流控芯片中深入研究LDLR对BCSC转移潜能的调控；（2）通过高通量蛋白质组学筛选LDLR下游底物分子，探讨潜在分子机制；（3）在BCSC肺转移小鼠模型中观察靶向膜蛋白LDLR对BCSC转移潜能的影响。本项目旨在利用微流控芯片能够动态监测细胞迁移的优势，阐明膜蛋白LDLR调控BCSC转移的功能及其机制，为开展针对BCSC的靶向治疗提供新的作用靶点。

Breast cancer stem cells (BCSCs) play critical roles in promoting breast cancer metastasis. Our recent study has shown that lipid metabolism is enriched in BCSC, and membrane protein LDLR is specifically highly expressed in BCSCs. Moreover, LDLR is correlated with the poor prognosis of breast cancer. However, if LDLR promotes BCSCs metastasis and how this process functions are still unclear. We speculate that membrane protein LDLR promote BCSCs metastasis by lipid metabolism. Our future works need to determine whether LDLR regulates the metastatic capability of BCSCs and investigate the molecular mechanism of that. Specifically, (1) In the optimized system of microfluidic chip, we need to assess the regulatory effects of LDLR on the metastatic capability of BCSCs; (2) We need to investigate the mechanism of how LDLR regulates metastatic capability of BCSCs through screening downstream molecular by high throughput proteomics; (3) We need to verify the correlation between LDLR and metastatic capability of BCSCs by targeting LDLR in the NOD/SCID mice model. Taken together, our study was designed to reveal the metastatic ability of BCSCs regulated by membrane protein LDLR and its possible mechanism by means of microfluidic chip, given its unique advantage of dynamic monitoring. Our findings may provide a rationale to develop applicable strategies to target BCSCs.