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rdf:type |
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lifeskim:mentions |
umls-concept:C0017636,
umls-concept:C0086418,
umls-concept:C0218504,
umls-concept:C0392756,
umls-concept:C0526871,
umls-concept:C0596290,
umls-concept:C1269955,
umls-concept:C1366765,
umls-concept:C1423596,
umls-concept:C1515844,
umls-concept:C1879547,
umls-concept:C2003941,
umls-concept:C2699153
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pubmed:issue |
1
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pubmed:dateCreated |
2007-12-24
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pubmed:abstractText |
Gliomas take a number of different genetic routes in the progression to glioblastoma multiforme, a highly invasive variant that is mostly unresponsive to current therapies. The alpha-chemokine stromal cell-derived factor (SDF)-1 alpha binds to the seven transmembrane G-protein-coupled CXCR-4 receptor and acts to modulate cell migration and proliferation by activating multiple signal transduction pathways. Leucine-rich repeats containing 4 (LRRC4), a putative glioma suppressive gene, inhibits glioblastoma cells tumorigenesis in vivo and cell proliferation and invasion in vitro. We also previously demonstrated that LRRC4 controlled glioblastoma cells proliferation by ERK/AKT/NF-kappa B signaling pathway. In the present study, we demonstrate that CXC chemokine receptor 4 (CXCR4) is expressed in human glioblastoma U251 cell line, and that SDF-1 alpha increases the proliferation, chemotaxis, and invasion in CXCR4+ glioblastoma U251 cells through the activation of ERK1/2 and Akt. The reintroduction of LRRC4 in U251 cells inhibits the expression of CXCR4 and SDF-1 alpha/CXCR4 axis-mediated downstream intracellular pathways such as ERK1/2 and Akt leading to proliferate, chemotactic and invasive effects. Furthermore, we provide evidence for proMMP-2 activation involvement in the SDF-1 alpha/CXCR4 axis-mediated signaling pathway. LRRC4 significantly inhibits proMMP-2 activation by SDF-1 alpha/CXCR4 axis-mediated ERK1/2 and Akt signaling pathway. Collectively, these results suggest a possible important "cross-talk" between LRRC4 and SDF-1 alpha/CXCR4 axis-mediated intracellular pathways that can link signals of cell proliferation, chemotaxis and invasion in glioblastoma, and may represent a new target for development of new therapeutic strategies in glioma.
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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 |
http://linkedlifedata.com/resource/pubmed/chemical/CXCL12 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CXCL12,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Precursors,
http://linkedlifedata.com/resource/pubmed/chemical/Extracellular Signal-Regulated MAP...,
http://linkedlifedata.com/resource/pubmed/chemical/Gelatinases,
http://linkedlifedata.com/resource/pubmed/chemical/LRRC4 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Matrix Metalloproteinase 9,
http://linkedlifedata.com/resource/pubmed/chemical/Metalloendopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, CXCR4,
http://linkedlifedata.com/resource/pubmed/chemical/progelatinase
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0730-2312
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pubmed:author |
pubmed-author:CaoLiL,
pubmed-author:ChenQiongQ,
pubmed-author:HuangChenC,
pubmed-author:LiDanD,
pubmed-author:LiGuiyuanG,
pubmed-author:LiXiaolingX,
pubmed-author:QiXiangX,
pubmed-author:ShenShourongS,
pubmed-author:TangKeK,
pubmed-author:TangYunlianY,
pubmed-author:WangDiD,
pubmed-author:WuMinghuaM,
pubmed-author:ZhouYanhongY
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pubmed:copyrightInfo |
Copyright (c) 2007 Wiley-Liss, Inc.
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
103
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
245-55
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:17549698-Cell Proliferation,
pubmed-meshheading:17549698-Chemokine CXCL12,
pubmed-meshheading:17549698-Chemotaxis,
pubmed-meshheading:17549698-Enzyme Activation,
pubmed-meshheading:17549698-Enzyme Precursors,
pubmed-meshheading:17549698-Extracellular Signal-Regulated MAP Kinases,
pubmed-meshheading:17549698-Gelatinases,
pubmed-meshheading:17549698-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:17549698-Glioblastoma,
pubmed-meshheading:17549698-Humans,
pubmed-meshheading:17549698-MAP Kinase Signaling System,
pubmed-meshheading:17549698-Matrix Metalloproteinase 9,
pubmed-meshheading:17549698-Metalloendopeptidases,
pubmed-meshheading:17549698-Mitogen-Activated Protein Kinase 1,
pubmed-meshheading:17549698-Mitogen-Activated Protein Kinase 3,
pubmed-meshheading:17549698-Neoplasm Invasiveness,
pubmed-meshheading:17549698-Nerve Tissue Proteins,
pubmed-meshheading:17549698-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:17549698-Receptors, CXCR4,
pubmed-meshheading:17549698-Tumor Cells, Cultured
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pubmed:year |
2008
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pubmed:articleTitle |
LRRC4 inhibits human glioblastoma cells proliferation, invasion, and proMMP-2 activation by reducing SDF-1 alpha/CXCR4-mediated ERK1/2 and Akt signaling pathways.
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pubmed:affiliation |
Cancer Research Institute, Central South University, 110# Xiang-Ya Road, Changsha, 410078 Hunan, People's Republic of China.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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