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Lysophosphatidic acid promotes cell invasion by up‐regulating the urokinase‐type plasminogen activator receptor in human gastric cancer cells
Author(s) -
Kim Mi Ha,
Park Jung Sun,
Chang Hee Jung,
Baek Min Kyung,
Kim Hyeong Rok,
Shin Boo Ahn,
Ahn Bong Whan,
Jung Young Do
Publication year - 2008
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.21696
Subject(s) - urokinase receptor , lysophosphatidic acid , rhoa , signal transduction , microbiology and biotechnology , cancer research , cancer cell , biology , receptor , cell migration , plasminogen activator , chemistry , cell , cancer , biochemistry , endocrinology , genetics
There is a strong correlation between the overexpression of urokinase‐type plasminogen activator receptor (uPAR) and gastric cancer invasion. This study examined the effect of phospholipid lysophosphatidic acid (LPA) on uPAR expression in human gastric cancer AGS cells and the underlying signal transduction pathways. Treating human gastric AGS cells with LPA induced the expression of uPAR mRNA and promoter activity in both a time‐ and dose‐dependent manner. Small interfering RNA targeting for LPA receptors, dominant negative Rho‐family GTPase (RhoA, Rac1, and Cdc42) and an expression vector encoding a mutated c‐jun (TAM67) partially blocked the LPA‐induced uPAR expression. Site‐directed mutagenesis and electrophoretic mobility shift studies showed that the transcription factors activation protein‐1 (AP‐1) and nuclear factor (NF)‐κB are essential for the LPA‐induced uPAR transcription. In addition, AGS cells treated with LPA showed enhanced invasion, which was partially abrogated by the uPAR‐neutralizing antibodies and inhibitors of Rho kinase, JNK, and NF‐κB. This suggests that LPA induces uPAR expression through the LPA receptors, Rho‐family GTPase, JNK, AP‐1 and NF‐κB signaling pathways, which in turn stimulates the cell invasiveness of human gastric cancer AGS cells. J. Cell. Biochem. 104: 1102–1112, 2008. © 2008 Wiley‐Liss, Inc.