Histone deacetylases 1, 6 and 8 are critical for invasion in breast cancer

Abstract

Abstract. Histone deacetylases (HDAcs) are associated with the development and progression of cancer, but it is not known which of the HDAc isoforms play important roles in breast cancer metastasis. This study identified the specific HDAC isoforms that are necessary for invasion and/or migration in human breast cancer cell lines. MDA-MB-231 cells were significantly more invasive and expressed higher levels of matrix metalloproteinase-9 (MMp-9) compared to McF-7 cells. We compared the expression of HDAc isoforms between McF-7 and MDA-MB-231 cells and found greater expression of HDAc4, 6 and 8 in MDA-MB-231 cells by rt-pcr and Western blot analyses. In addition, apicidin, a histone deacetylase inhibitor, was shown to attenuate the invasion, migration and MMP-9 expression in MDA-MB-231 cells. Using specific sirnAs directed against HDAc1, 4, 6 and 8, we show that inhibition of HDAc1, 6 and 8, but not HDAc4, are responsible for invasion and MMp-9 expression in MDA-MB-231 cells. We analyzed the invasiveness of McF-7 cells overexpressing HDAc1, 4, 6 or 8 and found that overexpression of HDAc1, 6 or 8 increased invasion and MMp-9 expression. By developing HDAc isoforms as potential biomarkers for breast cancer metastasis, the present study can be extended to developing therapies for breast cancer invasion.

Histone deacetylase 8 is deregulated in urothelial cancer but not a target for efficient treatment

“…Overexpression of HDAC8 has been reported in a considerable number of different cancer entities [26,34,36,37]. In neuroblastoma, in particular, HDAC8 expression was significantly correlated with further poor prognostic Figure 11 Compensation mechanism after HDAC8 knockdown in RT-112, VM-CUB1, SW-1710, 639-V and UM-UC-3 cells.…”

“…HDAC8 knockdown inhibits proliferation and enhances apoptosis in hepatocellular carcinoma cells via up-regulation of p53 [36]. In human breast cancer cell lines overexpression of HDAC1, HDAC6 or HDAC8 contributes to increased invasion and metalloproteinase-9 (MMP-9) expression [37]. Furthermore, HDAC8 promotes lung, colon and cervical cancer cell proliferation [31] and may regulate telomerase activity [38].…”

Limited efficacy of specific HDAC6 inhibition in urothelial cancer cells

“…10,26,27 Moreover, HDAC6 has been reported to be overexpressed in a number of different cancer types such as ovarian, gastric, and breast cancer, oral squamous carcinoma and acute myeloid leukemia. 11,[28][29][30][31] In bladder cancer, HDAC6 expression and function has scarcely been investigated. Our present study constitutes the first systematic study of HDAC6 expression and function in this tumor type allowing a first assessment of its potential as a therapeutic target.…”

DNA Methylation and Histone Deacetylation: Interplay and Combined Therapy in Cancer

“…HDAC8 has been found to be associated with various types of leukemia (Balasubramanian et al, 2008). HDAC1, 6 and 8 could also be important for breast cancer invasion (Park et al, 2011). These observations suggest that transcriptional repression of tumor-suppressor genes by overexpression or aberrant recruitment of HDACs to their promoter regions could be a common phenomenon in tumor onset and progression.…”