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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.

DACH1 inhibits breast cancer cell invasion and metastasis by down-regulating the transcription of matrix metalloproteinase 9