Aman Sattout, Li Yanan, Cheng Yunmeng, Yang Yuxi, Lv Linlin, Li Bowen, Xia Kangkai, Li Shujing, Wu Huijian
School of Bioengineering & Key Laboratory of Protein Modification and Disease, Liaoning Province, Dalian University of Technology, Dalian, China.
2 Ling Gong Road, Dalian, 116024, Liaoning, China.
Cell Death Discov. 2021 Nov 12;7(1):351. doi: 10.1038/s41420-021-00733-4.
Human Dachshund homolog 1 (DACH1) is usually defined as a tumor suppressor, which plays an influential role in tumor growth and metastasis in a variety of cancer cells. However, the underlying mechanisms in these process are not yet fully clarified. In this study, DACH1 inhibited the invasion and metastasis of breast cancer cells by decreasing MMP9 expression. Mechanistically, DACH1 represses the transcriptional level of MMP9 by interacting with p65 and c-Jun at the NF-κB and AP-1 binding sites in MMP9 promoter respectively, and the association of DACH1 and p65 promote the recruitment of HDAC1 to the NF-κB binding site in MMP9 promoter, resulting in the reduction of the acetylation level and the transcriptional activity of p65. Accordingly, the level of MMP9 was decreased. In conclusion, we found a new mechanism that DACH1 could inhibit the metastasis of breast cancer cells by inhibiting the expression of MMP9.
人类腊肠犬同源物1(DACH1)通常被定义为一种肿瘤抑制因子,它在多种癌细胞的肿瘤生长和转移中发挥着重要作用。然而,这些过程中的潜在机制尚未完全阐明。在本研究中,DACH1通过降低MMP9的表达来抑制乳腺癌细胞的侵袭和转移。机制上,DACH1分别通过在MMP9启动子的NF-κB和AP-1结合位点与p65和c-Jun相互作用,抑制MMP9的转录水平,并且DACH1与p65的结合促进HDAC1募集到MMP9启动子的NF-κB结合位点,导致p65的乙酰化水平和转录活性降低。相应地,MMP9的水平降低。总之,我们发现了一种新机制,即DACH1可通过抑制MMP9的表达来抑制乳腺癌细胞的转移。