乳腺癌是全球范围内女性健康的第一杀手。乳腺癌并非单一疾病，其分型复杂。其中雌激素受体ERα阳性(ERα+)但对激素替代治疗不敏感的乳腺癌，难于治疗且易发生转移，病人预后差。对这类乳腺癌的发生机制了解甚少，尚无动物体内模型用于机制和药物筛选上的研究。在前期研究中，我们发现全身性敲除新抑癌基因FRMD5可自发产生ERα+的小鼠乳腺癌。在本研究中，我们将在小鼠乳腺上皮细胞中条件性敲除FRMD5基因，研究FRMD5在诱导ERα+乳腺癌中的作用，并建立ERα+乳腺癌的小鼠模型，研究FRMD5-LATS1/YAP信号轴对ERα+乳腺癌产生的调控机制。利用所建立的ERα+小鼠乳腺癌模型，研究现有抗ERα+乳腺癌药物的效果并筛选新的药物前体；在病人中研究FRMD5功能缺失与ERα+乳腺癌病人预后判断的相关性；在ERα+乳腺癌的小鼠模型中研究靶向Hippo/YAP信号通路的抑制剂对ERα+乳腺癌的治疗作用。

Breast cancer is the number one killer of women's health worldwide. Breast cancer is not a single disease and its classification is complicated. Breast cancers with estrogen receptor ERα positive (ERα+) but not sensitive to hormone replacement therapy are difficult to treat and apt to metastasize, and usually the prognosis of patients is poor. However，little is known about the mechanism of this type of breast cancer，and no animal model has been available in the study of mechanism and drug screening. In the previous study, we found that knockout of FRMD5, a novel tumor suppressor gene, spontaneously produced ERα+ mouse breast cancer. In this study, we will knock out the FRMD5 gene in mouse mammary epithelial cells to investigate the role of FRMD5 in inducing ERα+ breast cancer and to establish a mouse model of ERα+ breast cancer，in which we will investigate the effect of FRMD5-LATS1/YAP signal axis on ERα+ breast cancer development. The established ERα+ mouse breast cancer model is used to study the effects of existing anti-ERα+ breast cancer drugs and to screen for novel drug precursors. In patients, we will investigate the correlation between the loss of FRMD5 function and the prognosis of ERα+ breast cancer patients. Therapeutic effect of inhibitors targeting the Hippo/YAP signaling pathway on ERα+ breast cancer is investigated in a mouse model of ERα+ breast cancer.