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Krüppel-like factor 9 down-regulates matrix metalloproteinase 9 transcription and suppresses human breast cancer invasion
Krüppel-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 inversel...
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Published in: | Cancer letters 2018-01, Vol.412, p.224-235 |
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Main Authors: | , , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Krüppel-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-κB p50/p65, which interacted with the NF-κB 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-κB targets, such as TNF-α, 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.
•KLF9 suppressed the migration and invasion of breast cancer cells.•MMP9 was a novel target of transcriptional factor KLF9.•KLF9 inhibited NF-κB/MMP9 pathway in breast cancer cells.•KLF9 suppressed the invasiveness of cancer cells through down-regulating MMP9 expression and activity.•KLF9 was inversely associated with MMP9 expression in breast cancer patients. |
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ISSN: | 0304-3835 1872-7980 |
DOI: | 10.1016/j.canlet.2017.10.027 |