Abstract:
:Epithelial-mesenchymal transition (EMT) is a critical early event in tumorigenesis. The contribution of heparan sulfate (HS) to EMT has not been fully elucidated. HS D-glucosaminyl 3-O-sulfotransferase-3B1 (3-OST-3B1) participates in the final step of HS fine structure biosynthesis, whose involvement in cancer has yet to be determined. This study demonstrated that following treatment with trichostatin-A, a histone deacetylase inhibitor, 3-OST-3B1 gene expression was activated in the pancreatic cancer cell line, PANC-1. By chromatin immunoprecipitation analysis, permissive histone modifications including an increase in histone H3 lysine 9 monoactylation (H3 ac K9) but a decrease in methylated histone H3 (H3 me K9) were observed accompanying transcriptional activation of 3-OST-3B1. Functional, results revealed that increased 3-OST-3B1 levels were involved in the promotion of EMT processes. In vitro studies demonstrated that overexpression of 3-OST-3B1 in both pancreatic cancer cells and vascular endothelial cells could trigger an EMT-like phenotype as evidenced by the up-regulation of Snail at the mRNA and protein level, and its nuclear translocation. And 3-OST-3B1 appeared to be sufficient for the development of a more mesenchymal phenotype in vivo. Together, the results from this study unveiled a distinct function for 3-OST-3B1 as an EMT inducer in cancer and provided a link between histone modification and EMT modulation.
journal_name
Cancer Biol Therjournal_title
Cancer biology & therapyauthors
Song K,Li Q,Jiang ZZ,Guo CW,Li Pdoi
10.4161/cbt.12.5.15957subject
Has Abstractpub_date
2011-09-01 00:00:00pages
388-98issue
5eissn
1538-4047issn
1555-8576pii
15957journal_volume
12pub_type
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