转移是乳腺癌患者死亡的主要原因。乳腺癌干细胞参与介导乳腺癌的转移复发，但调控乳腺癌干细胞转移潜能的信号网络和重要分子有待深入阐述和验证。我们前期研究揭示靶向p62信号蛋白可抑制乳腺癌干细胞的干性特征（Oncogene，2016年，已修回），新近发现其在乳腺癌临床肿瘤标本中高表达，干预p62可降低乳腺癌细胞系的致瘤性和侵袭能力，且高通量蛋白质谱组学鉴定提示p62信号蛋白与YBX1、DNAH9等分子存在相互作用。因此我们推测，p62信号蛋白与乳腺癌干细胞的转移密切相关。据此，本项目将借助微流控芯片实时、动态监测细胞运动的独特优势，阐述p62信号蛋白对乳腺癌干细胞转移潜能的调控作用，进一步运用实验动物模型及临床病理标本进行深入验证，并通过生物信息学分析及体外功能学实验探索可能的调控机制。本项目旨在明确p62信号蛋白在乳腺癌干细胞转移过程中的关键地位，为开展针对乳腺癌转移的靶向治疗提供科学依据。

Metastasis is the leading cause in breast cancer patient deaths. Breast cancer stem cells (BCSCs) play an important role in metastasis and recurrence. However, the detailed molecules and signaling networks remain further to be elucidated. Our previous data reveals that targeted intervention of p62 decreases stemness of BCSCs (Oncogene, 2016, revised). Recent work shows that p62 is highly expressed in breast cancer patient specimens, inhibition of p62 reduces tumorigenic and migration abilities of breast cancer cells, and mass spectrometry identification indicates that p62 binds with YBX1 and DNAH9. Thus we hypothesize that p62 is participated in BCSCs metastasis. In this project, by conduction of microfluidic system which can monitor tumor cells migration and metastasis in a real-time and dynamic manner, we try to explore the role of p62 in the regulation of BCSCs metastasis, further solidify our findings in mouse models and clinical specimens, and elucidate possible mechanisms by means of bioinformatics analysis and in intro functional assays. Collectively, our project aim to reveal the critical role of p62 in the regulation of BCSCs metastasis, which we believe will provide informative evidence for clinical application of breast cancer targeted therapy.