Abstract
Background:
Autotaxin (ATX) possesses lysophospholipase D (lyso PLD) activity, which converts lysophosphatidylcholine (LPC) into lysophosphatidic acid (LPA). The ATX-LPA signaling axis has been implicated in angiogenesis, chronic inflammation and tumor progression. Osteopontin (OPN) is an important chemokine involved in the survival, proliferation, migration, invasion and metastasis of gastric cancer cells. The focus of the present study was to investigate the relationship between the ATX-LPA axis and OPN.
Results:
In comparison with non-treated cells, we found that the ATX-LPA axis up-regulated OPN expression by 1.92-fold in protein levels and 1.3-fold in mRNA levels. The ATX-LPA axis activates LPA2, Akt, ERK and ELK-1 and also protects SGC7901 cells from apoptosis induced by Taxol treatment.
Conclusions:
This study provides the first evidence that expression of OPN induced by ATX-LPA axis is mediated by the activation of Akt and MAPK/ERK pathways through the LPA2 receptor. In addition, OPN is required for the protective effects of ATX-LPA against Taxol-induced apoptosis and ATX-LPA-induced migration of SGC7901 cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis / drug effects
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Cell Line, Tumor
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Cell Movement / drug effects
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Gene Expression / drug effects
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Humans
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Lysophospholipids / metabolism
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Multienzyme Complexes / genetics
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Multienzyme Complexes / metabolism*
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Osteopontin / genetics
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Osteopontin / metabolism*
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Paclitaxel / pharmacology
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Phosphodiesterase I / genetics
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Phosphodiesterase I / metabolism*
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Phosphoric Diester Hydrolases
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Protein Tyrosine Phosphatases / genetics
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Protein Tyrosine Phosphatases / metabolism
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Proto-Oncogene Proteins c-akt / genetics
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Proto-Oncogene Proteins c-akt / metabolism
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Pyrophosphatases / genetics
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Pyrophosphatases / metabolism*
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RNA, Messenger / analysis
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RNA, Messenger / biosynthesis
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Receptors, Lysophosphatidic Acid / genetics
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Receptors, Lysophosphatidic Acid / metabolism
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Signal Transduction* / drug effects
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Stomach Neoplasms / genetics
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Stomach Neoplasms / metabolism*
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Up-Regulation
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ets-Domain Protein Elk-1 / genetics
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ets-Domain Protein Elk-1 / metabolism
Substances
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ELK1 protein, human
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Lysophospholipids
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Multienzyme Complexes
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RNA, Messenger
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Receptors, Lysophosphatidic Acid
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ets-Domain Protein Elk-1
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Osteopontin
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Proto-Oncogene Proteins c-akt
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B59 protein, human
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Protein Tyrosine Phosphatases
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Phosphoric Diester Hydrolases
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Phosphodiesterase I
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alkylglycerophosphoethanolamine phosphodiesterase
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Pyrophosphatases
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Paclitaxel
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lysophosphatidic acid