Heparan sulfate D-glucosaminyl 3-O-sulfotransferase-3B1, a novel epithelial-mesenchymal transition inducer in pancreatic cancer

Cancer Biol Ther. 2011 Sep 1;12(5):388-98. doi: 10.4161/cbt.12.5.15957. Epub 2011 Sep 1.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Azacitidine / analogs & derivatives
  • Azacitidine / pharmacology
  • Base Sequence
  • Cell Line, Tumor
  • Chromatin Immunoprecipitation
  • Decitabine
  • Endothelial Cells / cytology
  • Epithelial-Mesenchymal Transition* / drug effects
  • Heparitin Sulfate / biosynthesis
  • Histones / metabolism
  • Humans
  • Hydroxamic Acids / pharmacology
  • Methylation / drug effects
  • Pancreatic Neoplasms / enzymology*
  • Pancreatic Neoplasms / genetics
  • RNA, Messenger / biosynthesis
  • Sequence Analysis, DNA
  • Snail Family Transcription Factors
  • Sulfotransferases / genetics
  • Sulfotransferases / metabolism*
  • Transcription Factors / biosynthesis
  • Transcription Factors / genetics
  • Transcriptional Activation


  • Histones
  • Hydroxamic Acids
  • RNA, Messenger
  • Snail Family Transcription Factors
  • Transcription Factors
  • trichostatin A
  • Decitabine
  • Heparitin Sulfate
  • Sulfotransferases
  • heparan sulfate D-glucosaminyl 3-O-sulfotransferase
  • Azacitidine