基底型三阴性乳腺癌（通常ER、PR、Her-2均为阴性，简称BLBC）在乳腺癌患者中大约占15%，而且患者预后极差，生存时间短。目前对于BLBC仍缺乏有效的靶向治疗。我们前期研究发现KLF5转录因子促进BLBC生长，是有效治疗靶点，但是其上游调节机制不清楚。我们发现细胞命运决定因子DACH1在BLBC细胞中可能通过抑制YB1转录因子,下调KLF5及其下游靶基因的表达并抑制细胞增殖，诱导细胞凋亡。为了证明这个假设，我们计划首先明确DACH1和YB1体内外调节BLBC的功能，然后解析DACH1通过YB1抑制KLF5的分子机制，最后用免疫组织化学染色方法检测DACH1、YB1和KLF5等在乳腺癌样本中表达以明确它们的临床意义。本研究旨在明确DACH1抑肿瘤的功能和分子机制及发现新的治疗靶点。

Basal-like triple negative breast cancer (BLBC, ER,PR,Her-2 negative) accouts for around 15% of all breast cancer cases and there are no effective targeted therapies. The BLBC patients have shortest survival rate. Our previous study demonstrated that KLF5 promotes BLBC cell proliferation and tumor growth and is an effective therapeutic target. Recently, we found that cell fate determination factor DACH1 significantly downregulates the expression levels of KLF5 and its downstream target genes through inhibiting the YB1 transcription factor. We hypothesize that DACH1 inhibits BLBC through inhibiting the transcription of KLF5 via YB1. First, we will determine the functions of DACH1 and YB1 in BLBC in vitro and in vivo. Second, we will characterize the mechanism by which DACH1 suppresses KLF5 through YB1 in BLBC. Finally, we will examine the expression correlation between the DACH1, YB1 and KLF5 by immunohistochemistry in human BLBC samples. The success of this project will figure out the function and mechanism of DACH1 in BLBC and provide novel prognosis biomarkers and therapeutic targets for BLBC treatment.