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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
2010-1-25
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pubmed:abstractText |
Peritoneal carcinomatosis is a frequent finding in gastric cancer associated with a poor prognosis. The features that enable gastric tumors to disseminate are poorly understood until now. Previously, we showed elevated mRNA levels of phosphoglycerate kinase 1 (PGK1), an adenosine triphosphate-generating enzyme in the glycolytic pathway, the chemokine receptor 4 (CXCR4), the corresponding chemokine ligand 12 (CXCL12) and beta-catenin in specimens from gastric cancer patients with peritoneal carcinomatosis. In this study, the influence of PGK1 on CXCR4 and beta-catenin was assessed as well as the invasiveness of PGK1 overexpressing cancer cells. In this current study, we found that PGK1 regulates the expression of CXCR4 and beta-catenin at the mRNA and protein levels. On the other hand, CXCR4 regulates the expression of PGK1. Plasmid-mediated overexpression of PGK1 dramatically increased the invasiveness of gastric cancer cells. Interestingly, inhibition of CXCR4 in cells overexpressing PGK1 produced only a moderate reduction of invasiveness suggesting that, PGK1 itself has a critical role in tumor invasiveness. Immunohistochemistry in specimens from diffuse gastric cancer patients also revealed an overexpression of PGK1 in patients with development of peritoneal carcinomatosis. Therefore, PGK1 may be a crucial enzyme in peritoneal dissemination. Together these findings suggest that the enhanced expression of PGK1 and its signaling targets CXCR4 and beta-catenin in gastric cancer cells promote peritoneal carcinomatosis. Thus, PGK1 may serve as prognostic marker and/or be a potential therapeutic target to prevent dissemination of gastric carcinoma cells into the peritoneum.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/19688824-10200776,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19688824-10527450,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19688824-10987283,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19688824-11175802,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19688824-11272277,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19688824-11792709,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19688824-11846609,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19688824-11912162,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19688824-12174867,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19688824-12176869,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19688824-13351639,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19688824-14672915,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19688824-15053920,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19688824-16048908,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19688824-16230077,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19688824-16489019,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19688824-16493704,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19688824-16651426,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19688824-17210694,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19688824-17724466,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19688824-18453750,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19688824-18553401,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19688824-18720530,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19688824-9826536
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
1097-0215
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pubmed:author |
pubmed-author:BühlerSarahS,
pubmed-author:BeckertStefanS,
pubmed-author:BrücherBjörn L D MBL,
pubmed-author:GaedckeJochenJ,
pubmed-author:KönigsrainerAlfredA,
pubmed-author:KönigsrainerIngmarI,
pubmed-author:LöfflerMarkusM,
pubmed-author:NieseltKayK,
pubmed-author:NorthoffHinnakH,
pubmed-author:TaichmanRussell SRS,
pubmed-author:TraubFrankF,
pubmed-author:TritschlerIsabelI,
pubmed-author:WellerMichaelM,
pubmed-author:ZiekerDerekD
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pubmed:issnType |
Electronic
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pubmed:day |
15
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pubmed:volume |
126
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1513-20
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pubmed:dateRevised |
2011-7-26
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pubmed:meshHeading |
pubmed-meshheading:19688824-Blotting, Western,
pubmed-meshheading:19688824-Cell Line, Tumor,
pubmed-meshheading:19688824-Cell Movement,
pubmed-meshheading:19688824-Cell Survival,
pubmed-meshheading:19688824-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:19688824-Humans,
pubmed-meshheading:19688824-Immunohistochemistry,
pubmed-meshheading:19688824-Models, Biological,
pubmed-meshheading:19688824-Peritoneal Neoplasms,
pubmed-meshheading:19688824-Phosphoglycerate Kinase,
pubmed-meshheading:19688824-RNA Interference,
pubmed-meshheading:19688824-Receptors, CXCR4,
pubmed-meshheading:19688824-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:19688824-Signal Transduction,
pubmed-meshheading:19688824-Stomach Neoplasms,
pubmed-meshheading:19688824-beta Catenin
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pubmed:year |
2010
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pubmed:articleTitle |
Phosphoglycerate kinase 1 a promoting enzyme for peritoneal dissemination in gastric cancer.
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pubmed:affiliation |
Department of General Visceral, Transplant Surgery Comprehensive Cancer Center, University of Tuebingen, D-72076 Tuebingen, Germany. derek.zieker@med.uni-tuebingen.de
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, N.I.H., Extramural
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