肿瘤干细胞在乳腺癌复发转移中发挥重要作用。细胞极性蛋白Rich1的表达缺失与上皮细胞恶性转化密切相关，其确切作用机制有待深入研究。我们前期发现，Rich1在乳腺癌组织中的低表达与患者的不良预后显著相关，下调Rich1能促进乳腺癌干细胞样特性的获得，下调TAZ的磷酸化水平，Rich1与Amot-p80、Merlin可能存在着相互作用。故提出假设：Rich1可通过与Merlin竞争性结合Amot-p80，激活Hippo通路，下调YAP/TAZ介导的转录活性，抑制肿瘤干细胞样特性及乳腺癌的恶性进程。我们拟用临床组织标本，明确Rich1在乳腺癌的表达及其临床意义；利用细胞和动物模型，采用CRISPR、Co-IP等细胞分子生物学手段，探讨Rich1异常表达对乳腺癌干细胞样特性的调控作用及机制。该项目的完成，将阐明Rich1异常表达在乳腺癌恶性进程中的全新作用机制，为抗乳腺癌侵袭转移治疗提供理论依据。

Cancer stem cells play an important role in the recurrence and metastasis of breast cancer. Rich1 is an important cell polarity protein. Its expression deficiency is closely related to the malignant transformation of epithelial cells. However, the exact role of Rich1 in breast cancer and the potential mechanism need to be further studied. Based on our previous studies, the low expression of Rich1 in breast cancer tissues was significantly associated with poor prognosis. Downregulation of Rich1 could promote the acquisition of stem cell-like characteristics of breast cancer and significantly reduce the phosphorylation level of TAZ. Rich1 may interact with Merlin. Thus, we hypothesized that Rich1 can inhibit the malignant process of breast cancer by interacting with Merlin to activate Hippo pathway, down-regulate YAP/TAZ-mediated transcriptional activity and inhibit stem cell-like characteristics. We intend to clarify the expression of Rich1 in breast cancer and its clinical significance by clinical tissue specimens. Using CRISPR, CO-IP and other cell and molecular biological methods in cell and animal models, we aim to explore the regulatory role of Rich1 on stem cell-like characteristics of breast cancer and its specific mechanisms. The completion of this project will clarify the new mechanism of Rich1 abnormal expression in the malignant process of breast cancer, and provide theoretical basis for anti-invasion and metastasis treatment of breast cancer.