Down-regulation of matrix metalloproteinase-7 inhibits metastasis of human anaplastic thyroid cancer cell line

Epigenetic drugs such as histone deacetylase inhibitors (HDACIs) possess anticancer properties due to its ability to regulate genes associated with tumor growth, differentiation, apoptosis and metastasis. In addition to its apoptotic effect, phenylbutyrate (PB), a carboxylic acid HDACI, inhibited an...

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Bibliographic Details
Published in:Clinical & experimental metastasis 2012-01, Vol.29 (1), p.71-82
Main Authors: Chen, Szu-Tah, Liu, Dah-Wel, Lin, Jen-Der, Chen, Fang-Wu, Huang, Yu-Yao, Hsu, Brend Ray-Sea
Format: Article
Language:English
Subjects:
Acetylation
Animals
Base Sequence
Biomedical and Life Sciences
Biomedicine
Blotting, Western
Cancer Research
Cell Line, Tumor
DNA Primers
Down-Regulation
Female
Gene Knockdown Techniques
Hematology
Histones - metabolism
Humans
Matrix Metalloproteinase 7 - genetics
Matrix Metalloproteinase 7 - metabolism
Mice
Mice, SCID
Neoplasm Metastasis - prevention & control
Oncology
Phosphorylation
Research Paper
Reverse Transcriptase Polymerase Chain Reaction
Surgical Oncology
Thyroid Neoplasms - enzymology
Thyroid Neoplasms - pathology
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Summary:Epigenetic drugs such as histone deacetylase inhibitors (HDACIs) possess anticancer properties due to its ability to regulate genes associated with tumor growth, differentiation, apoptosis and metastasis. In addition to its apoptotic effect, phenylbutyrate (PB), a carboxylic acid HDACI, inhibited an anaplastic (ATC) thyroid cancer cell line ARO from penetrating a matrigel coated transwell with concomitant suppression of a metastasis-associated gene, matrix metalloproteinase-7 (MMP-7) and stimulation of a transformation suppressor protein, reversion-inducing- cysteine-rich protein with Kazal motifs without affecting MMP-2 expression levels. Direct evidence suggesting MMP-7 down-regulated cancer metastasis came from the observation of a decreased pulmonary metastasis in SCID mice xeno-transplanted with MMP-7-knocked-down ARO cells. In addition, H-89, a protein kinase A inhibitor, remarkably restored the down-regulaed MMP-7 level treated by PB. Thus, the suppressive effect of PB on MMP-7 was partially carried out through H3 phosphoacetylation. To conclude, our findings suggest PB inhibits MMP-7 expression epigenetically through phosphoacetylation of histone proteins, and thereby, reduced invasive ability of an ATC thyroid cancer cell line.
ISSN:0262-0898
1573-7276
DOI:10.1007/s10585-011-9430-8