Down-regulation of matrix metalloproteinase-7 inhibits metastasis of human anaplastic thyroid cancer cell line
Resource
Clin. Exp. Metastasis, 29(1), 71-82
Journal
Clinical & Experimental Metastasis
Pages
71-82
Date Issued
2012
Date
2012
Author(s)
Chen, Szu-Tah
Liu, Dah-Wel
Lin, Jen-Der
Chen, Fang-Wu
Huang, Yu-Yao
Hsu, Brend Ray-Sea
Abstract
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.
Subjects
Thyroid cancer
MMP-7
Metastasis
Phenylbutyrate
siRNA
SDGs
Other Subjects
arylbutyric acid derivative; histone deacetylase inhibitor; histone H3; matrilysin; phenylbutyrate; unclassified drug; histone; matrilysin; primer DNA; anaplastic carcinoma; animal experiment; animal model; apoptosis; article; cancer cell culture; controlled study; down regulation; drug effect; drug mechanism; female; gene repression; human; human cell; human tissue; metastasis; metastasis inhibition; mouse; nonhuman; thyroid cancer; acetylation; animal; down regulation; enzymology; gene silencing; genetics; metabolism; metastasis; mouse mutant; nucleotide sequence; pathology; phosphorylation; reverse transcription polymerase chain reaction; thyroid tumor; tumor cell line; Western blotting; Acetylation; Animals; Base Sequence; Blotting, Western; Cell Line, Tumor; DNA Primers; Down-Regulation; Female; Gene Knockdown Techniques; Histones; Humans; Matrix Metalloproteinase 7; Mice; Mice, SCID; Neoplasm Metastasis; Phosphorylation; Reverse Transcriptase Polymerase Chain Reaction; Thyroid Neoplasms
File(s)![Thumbnail Image]()
Loading...
Name
index.html
Size
23.17 KB
Format
HTML
Checksum
(MD5):367e6c00a0c23539866941bbf065c5ec