title: Heparan sulfate D-glucosaminyl 3-O-sulfotransferase-3B1, a novel epithelial-mesenchymal transition inducer in pancreatic cancer.
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.
authors.affiliation: China Pharmaceutical University, Nanjing, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Song
authors.forename: Qin
authors.initials: Q
authors.lastname: Li
authors.forename: Zhen-Zhen
authors.initials: ZZ
authors.lastname: Jiang
authors.forename: Chao-Wei
authors.initials: CW
authors.lastname: Guo
authors.forename: Ping
authors.initials: P
authors.lastname: Li
mesh_terms: D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D001483:Base Sequence; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D000077209:Decitabine; D042783:Endothelial Cells / Q000166:cytology; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D006497:Heparan Sulfate / Q000096:biosynthesis; D006657:Histones / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D008745:Methylation / Q000187:drug effects; D010190:Pancreatic Neoplasms / Q000201:enzymology* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D017422:Sequence Analysis, DNA; D000071250:Snail Family Transcription Factors; D015238:Sulfotransferases / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D015533:Transcriptional Activation
chemical_list: D001374:Azacitidine; D000077209:Decitabine; D006497:Heparan Sulfate; D006657:Histones; D006877:Hydroxamic Acids; D012333:RNA, Messenger; D000071250:Snail Family Transcription Factors; D015238:Sulfotransferases; D014157:Transcription Factors; C012589:trichostatin A; C102180:heparan sulfate D-glucosaminyl 3-O-sulfotransferase