我们报道了DEC1表达上调与乳腺癌恶性表型相关, 并发现其在三阴性乳腺癌中表达明显高于其它分子亚型。干扰内源性DEC1可从mRNA和蛋白水平上调claudin-1，-4，-7并阻止由TGF-β诱导的EMT表型，进而抑制乳腺癌细胞的侵袭能力。但DEC1对于claudins的具体调控机制不清。通过序列分析对比，我们推测DEC1通过其BHLH功能域识别和结合claudins启动子区E-box元件以抑制其转录，从而促进EMT并上调乳腺癌的侵袭转移。我们拟通过双向调控乳腺癌细胞系中DEC1的表达，分别构建并转染DEC1和claudins的突变体质粒，应用ChIP、荧光素酶报告基因、PCR、免疫印迹、Transwell及裸鼠移植等方法，阐明DEC1下调claudins转录的分子机制及对乳腺癌细胞侵袭转移的影响,为寻找乳腺癌新的治疗靶点提供依据。

We reported that the overexpression of Differentiated embryo-chondrocyte-expressed gene 1 (DEC1) was correlated with the malignant phenotype in breast cancer. In our preliminary study, we found DEC1 was overexpressed in the Triple-negative breast cancer compared with other types of breast cancer. In addition, DEC1 knockdown by siRNA could enhance the transcription of claudin-1，-4，-7 and in turn reverse the EMT phenotype induced by TGF-β and attenuate the invasion and metastasis of breast cancer. We analyzed the promoter region of claudins and found E-box motifs which can be recognized by DEC1. We hypothesize that DEC1 inhibits the transcription of claudins through binding to the E-box motif in the promoter region of claudins. To test our hypothesis，we will bidirectionally regulate the transcription of DEC1 and also overexpress E-box-binding deficient mutants in multiple breast cancer cell lines. By adopting ChIP, luciferase reporter assay, PCR, IB, Transwell and nude mouse model, we will try to clarify the detailed mechanism by which DEC1 regulates claudins and enhances the invasion and metastasis in breast cancer. Based on these studies, we hope to find potential targets for molecular therapy and drug design, and further provide theoretical and experimental basis for individual treatment to breast cancer.