研究证实在多种类型肿瘤细胞中发现一群能够休眠和早期播散的细胞，这类细胞能幸免于肿瘤的常规药物治疗和靶向治疗，称为休眠干细胞。它们是怎样维持休眠又是如何被“唤醒”？探讨这一过程的分子机制是目前研究肿瘤复发与转移的热点。申请者前期构建稳定传代的乳腺癌干细胞株（中国专利，201510330647.5），证实LGR5与乳腺癌患者临床预后相关，过表达LGR5可促进乳腺癌干细胞的侵袭与转移（Stem Cells，2015），进一步研究发现LGR5在代谢活跃的乳腺癌干细胞中表达显著增加，且LGR5高表达的乳腺癌患者更早出现复发。由此我们提出科学假说：LGR5可能参与加速乳腺癌复发转移及起始休眠干细胞增殖的调控过程。本项目拟采用体内动物成像技术研究LGR5调控乳腺癌干细胞休眠作用；通过基因芯片筛查和一系列实验阐明LGR5调控乳腺癌干细胞休眠的分子机制，为乳腺癌发病机制提供新的理论依据和治疗靶点。

Tumour dormancy has been recognized as a clinical phenomenon in numerous types of cancer for many years because the disseminated stem cells can enter dormancy and become refractory to targeted or conventional therapies. But regulation of the switch from quiescent dormancy to active regrowth is poorly understood, this poses a tremendous challenge to the researchers. Applicant had proved that LGR5 significantly Tumour dormancy has been recognized as a clinical phenomenon in numerous types of cancer for many years because the disseminated stem cells can enter dormancy and become refractory to targeted or conventional therapies. But regulation of the switch from quiescent dormancy to active regrowth is poorly understood, this poses a tremendous challenge to the researchers. Applicant had proved that LGR5 significantly associated with recurrence and poor outcome in breast cancer, LGR5 promoted cell mobility, tumour formation, and epithelial-mesenchymal transition by activating Wnt/β -catenin signaling (Stem cells, 2015). In addition, LGR5 was specificity expressed in the active proliferation stem cells when study in well builded stem cell lines (patent NO. 201510330647.5), and LGR5 overexpression in breast cancer predicted short disease-free survival period. Thus, We put forward the scientific hypothesis: LGR5 is required for dormant tumour stem cell reactivation and boosted tumour recurrence. This project aims to study the potential roles of LGR5 in breast cancer stem cell dormancy and reactivation in noninvasive imaging models; use the microarray gene chips and experimental studies of mechanisms, and provide an experimental basis for the development of breast cancer and targeted therapy.