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Lysophosphatidic acid signaling through LPA receptor subtype 1 induces colony scattering of gastrointestinal cancer cells

Cited 15 time in Web of Science Cited 16 time in Scopus
Authors
Shin, Kum-Joo; Kim, You Lim; Lee, Sukmook; Kim, Dong-Kyu; Ahn, Curie; Chung, Junho; Seong, Jae Young; Hwang, Jong-Ik
Issue Date
2008-07-02
Publisher
Springer Verlag
Citation
J Cancer Res Clin Oncol. 135(1):45-52
Keywords
Blotting, WesternExtracellular Signal-Regulated MAP Kinases/metabolismGastrointestinal Neoplasms/genetics/*metabolism/pathologyHumansLentivirus/geneticsLysophospholipids/*metabolismRNA, Messenger/genetics/metabolismRNA, Small Interfering/pharmacologyReceptors, Lysophosphatidic Acid/*genetics/metabolismReverse Transcriptase Polymerase Chain Reaction*Signal TransductionTumor Cells, Cultured
Abstract
PURPOSE: Lysophosphatidic acid (LPA) is a multifunctional lipid mediator involved in triggering tumor cell invasion and metastasis, as well as malignant cell growth. LPA is also known to modulate the colony scattering of epithelial cancers, which is a prerequisite for cell invasion. However, the underlying details of how this is accomplished are not clear. Here we have investigated the roles of specific LPA receptor subtypes in cell scattering. METHODS: Gastrointestinal carcinoma cell lines were examined for cell scattering activity in response to LPA, and the expression of LPA receptor subtypes was determined by RT-PCR. The effect of down regulation of each LPA receptor in DLD1 cells was determined using a shRNA-lentivirus system. In addition, the effect of overexpression of LPA receptors on cell scattering was investigated using lentivirus expression constructs. RESULTS: The colonies of AGS and DLD1, but not MKN74, cells were dispersed in response to LPA. RT-PCR analysis revealed that the mRNAs of LPA1, LPA2, and LPA3 were present in AGS and DLD1 cells, but only LPA2 mRNA was detected in MKN74 cells. In DLD1 cells, the scattering activity induced by LPA was partially blocked by pretreatment with PP2 and PD98059, inhibitors of src kinase and MEK, respectively. LPA1 knockdown with shRNA decreased the degree of cell scattering induced by LPA. Knockdown of LPA2 or LPA3 had no effect on LPA-induced scattering. In addition, overexpression of LPA1 in DLD1 cells slightly decreased the response time of LPA-induced cell scattering. On the contrary, MKN74 cells expressing exogenous LPA1 did not respond to LPA by scattering. CONCLUSION: These results demonstrate that LPA1 mediates LPA-stimulated cell scattering of gastrointestinal carcinomas, but that activation of other intracellular pathways, besides those contributing to ERK phosphorylation, is also necessary for cell scattering in response to LPA.
ISSN
0171-5216 (Print)
Language
English
URI
http://www.springerlink.com/content/6421838t722w03tx/fulltext.pdf

http://hdl.handle.net/10371/67517
DOI
https://doi.org/10.1007/s00432-008-0441-z
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College of Medicine/School of Medicine (의과대학/대학원)Dept. of Biochemistry & Molecular Biology (생화학교실)Journal Papers (저널논문_생화학교실)
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