三阴性乳腺癌(TNBC)缺乏有效的分子靶点，预后差；因此，探索TNBC关键信号通路尤其重要。DACH1与乳腺癌干性、EMT和转移相关，其低表达预示患者预后不良。TNBC细胞系和瘤组织中DACH1的表达基本丢失, 但与TNBC的确切关系仍不明确。TNBC中EGFR-STAT3活化增加干性、侵袭、转移和治疗抗性。大数据分析和前期实验提示DACH1与EGFR-STAT3信号之间负相关, 其相互作用未见研究报告。我们推测两个信号间功能失衡是TNBC恶性生物学的重要因素之一。通过调节DACH1或EGFR-STAT3的相对表达，观察TNBC细胞增殖、干性、EMT、侵袭、致瘤性及治疗敏感性；报告基因和免疫沉淀分析DACH1与STAT3结合的分子基础；评价乳腺癌组织DACH1和EGFR-STAT3信号表达与病理-临床特征的关系。研究结果将丰富TNBC信号网络间交互调节，为乳腺癌靶向治疗提供科学依据。

Comparing with other types of breast cancer, triple negative breast cancer (TNBC) has a worse prognosis for lack of effective molecular target therapy; therefore, it is vital important to explore the key signaling driving the initiation and progression of TNBC. DACH1 has been shown to regulate breast cancer stemness, EMT and metastasis, and its lower expression is associated with unfavorite prognosis. The expression of DACH1 is barely detected in both TNBC cell lines and tumor tissues; however, its role in TNBC has not been clearly elucidated. Hyper-activation of EGFR-STAT3 signaling is a basic characteristic of TNBC, leading to the stemness, invasion, metastasis and therapeutic resistance to chemotherapy and radiotherapy..Analysis of open gene expression databases and preliminary experiments suggested a significant association between DACH1 and EGFR-STAT3, so far, reciprocal regulation of DACH1 with EGFR-STAT3 has not been reported. Hereby, we proposed that unbalanced function of DACH1 and EGFR-STAT3 attribute to the malignant behaviors of TNBC. By modifying the relative expressions of DACH1 or EGFR-STAT3 through ectopic expression or shRNA-based gene silencing, the proliferation, stemness, EMT, invasion, tumorigenesis and sensitivity to chemotherapy/radiotherapy will be determined; Luciferase-based promoter analysis and chromatin immunoprecipitation will be applied to evaluate the association of DACH1 with EGFR and STAT3; The relationships between DACH1 and EGFR-STAT3 signaling with clinic-pathological parameters, such as tumor size, tissue differentiation, lymph node involvement, TNM stage and prognosis will be systematically analyzed. Altogether, our results will deepen the understanding of cross-talk among various signaling in TNBC, providing a molecular basis for precision target therapy. ...Keywords: Breast cancer, EGFR, STAT3, Stemness, EMT