| http://purl.uniprot.org/citations/24146905 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/24146905 | http://www.w3.org/2000/01/rdf-schema#comment | "Trypsin or Tumor associated trypsin (TAT) activation of Protease-activated receptor 2 (PAR-2) promotes tumor cell proliferation in gastrointestinal cancers. The role of the trypsin/PAR-2 network in esophageal adenocarcinoma (EA) development has not yet been investigated. The aim of this study is to investigate the role of trypsin/PAR-2 activation in EA tumorogenesis and therapy. We found that esophageal adenocarcinoma cells (EACs) and Barrett's Metaplasia (BART) expressed high levels of type 3 extra-pancreatic trypsinogen (PRSS3), a novel type of TAT. Activity of secreted trypsin was detected in cultured media from EA OE19 and OE33 cultures but not from BART culture. Surface PAR-2 expression in BART and EACs was confirmed by both flow cytometry and immunofluorescence. Trypsin induced cell proliferation (~ 2 fold; P<0.01) in all tested cell lines at a concentration of 10 nM. Inhibition of PAR-2 activity in EACs via the PAR-2 antagonist ENMD (500 µM), anti-PAR2 antibody SAM-11 (2 µg/ml), or siRNA PAR-2 knockdown, reduced cell proliferation and increased apoptosis by up to 4 fold (P<0.01). Trypsin stimulation led to phosphorylation of ERK1/2, suggesting involvement of MAPK pathway in PAR-2 signal transduction. Inhibition of PAR-2 activation or siRNA PAR-2 knockdown in EACs prior to treatment with 5 FU reduced cell viability of EACs by an additional 30% (P<0.01) compared to chemotherapy alone. Our data suggest that extra-pancreatic trypsinogen 3 is produced by EACs and activates PAR-2 in an autocrine manner. PAR-2 activation increases cancer cell proliferation, and promotes cancer cell survival. Targeting the trypsin activated PAR-2 pathway in conjunction with current chemotherapeutic agents may be a viable therapeutic strategy in EA."xsd:string |
| http://purl.uniprot.org/citations/24146905 | http://purl.org/dc/terms/identifier | "doi:10.1371/journal.pone.0076667"xsd:string |
| http://purl.uniprot.org/citations/24146905 | http://purl.uniprot.org/core/author | "Han S."xsd:string |
| http://purl.uniprot.org/citations/24146905 | http://purl.uniprot.org/core/author | "Hughes S.J."xsd:string |
| http://purl.uniprot.org/citations/24146905 | http://purl.uniprot.org/core/author | "Lee C.W."xsd:string |
| http://purl.uniprot.org/citations/24146905 | http://purl.uniprot.org/core/author | "Sarosi G.A. Jr."xsd:string |
| http://purl.uniprot.org/citations/24146905 | http://purl.uniprot.org/core/author | "Trevino J.G."xsd:string |
| http://purl.uniprot.org/citations/24146905 | http://purl.uniprot.org/core/date | "2013"xsd:gYear |
| http://purl.uniprot.org/citations/24146905 | http://purl.uniprot.org/core/name | "PLoS One"xsd:string |
| http://purl.uniprot.org/citations/24146905 | http://purl.uniprot.org/core/pages | "e76667"xsd:string |
| http://purl.uniprot.org/citations/24146905 | http://purl.uniprot.org/core/title | "Autocrine extra-pancreatic trypsin 3 secretion promotes cell proliferation and survival in esophageal adenocarcinoma."xsd:string |
| http://purl.uniprot.org/citations/24146905 | http://purl.uniprot.org/core/volume | "8"xsd:string |
| http://purl.uniprot.org/citations/24146905 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/24146905 |
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