Abstract:
:Histone deacetylases (HDACs) are important in chromatin remodeling and epigenetic regulation of gene expression. Histone deacetylase inhibitors (HDACi) have highly effective anti-metastatic and anti-angiogenic activity in various types of cancer, while the molecular mechanisms involved in this process are not fully understood. In the present study, trichostatin A (TSA), a HDACi, was found to suppress MCF-7 breast carcinoma cell invasion and upregulate TET1 expression in a dose-dependent manner. TET1, a dioxygenase involved in cytosine demethylation, is downregulated during breast cancer progression. TET1 knockdown in MCF-7 cells facilitates cell invasion, inhibits the expression of tissue inhibitors of metalloproteinase 2/3 (TIMP2/3) and promotes matrix metalloproteinases (MMP) 2/9 transcriptional activity. Importantly, TET1 depletion impaired the inhibitory effect of TSA on breast cancer cell invasion. Together, these results illustrated a mechanism by which TET1 partially mediates HDACi elicited suppression of breast cancer invasion.
journal_name
Mol Med Repjournal_title
Molecular medicine reportsauthors
Lu HG,Zhan W,Yan L,Qin RY,Yan YP,Yang ZJ,Liu GC,Li GQ,Wang HF,Li XL,Li Z,Gao L,Chen GQdoi
10.3892/mmr.2014.2517subject
Has Abstractpub_date
2014-11-01 00:00:00pages
2595-600issue
5eissn
1791-2997issn
1791-3004journal_volume
10pub_type
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