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论文类型：期刊论文

发表时间：2018-01-01

发表刊物：CANCER LETTERS

收录刊物：SCIE、PubMed

卷号：412

期号：412

页面范围：224-235

ISSN号：0304-3835

关键字：Kruppel-like factor 9; Matrix metalloproteinase 9; Human breast cancer; Invasion; Metastasis

摘要：Kruppel-like factor 9 (KLF9) plays critical roles in several types of tumor. However, the biological functions and the underlying mechanisms of KLF9 in breast cancer metastasis are still unknown. Here, we found the expression of KLF9 was significantly down-regulated in breast cancer and was inversely correlated with the expression of matrix metalloproteinase 9 (MMP9) in breast cancer patients. Functionally, KLF9 transcriptionally down-regulated MMP9 expression and inhibited the metastasis of breast cancer cells. Mechanistically, KLF9 repressed human MMP9 promoter activity by binding to the CACCC motif and interacting with NF-kappa B p50/p65, which interacted with the NF-kappa B response element of the MMP9 promoter, leading to decreased expression of MMP9. In the context of breast cancer, KLF9 promoted the accumulation of HDAC1, thereby decreasing the acetylation of the KLF9-binding site on the MMP9 promoter, and this might be the molecular basis of KLF9-mediated inhibition of MMP9 transcription. In addition to MMP9, KLF9 also down-regulated several other NF-kappa B targets, such as TNF-alpha, VEGFA and uPA in breast cancer cells. Taken together, these results uncovered a new mechanism by which KLF9 could down-regulate MMP9 expression to inhibit breast cancer metastasis. (C) 2017 Elsevier B.V. All rights reserved.