title: Lysophosphatidic acid stimulates gastric cancer cell proliferation via ERK1-dependent upregulation of sphingosine kinase 1 transcription.
abstract: In MKN1 gastric cancer cells, lysophosphatidic acid (LPA) upregulates expression of sphingosine kinase 1 (SphK1) and its downregulation or inhibition suppresses LPA mediated proliferation. Although LPA activates numerous signaling pathways downstream of its receptors, including extracellular-signal-regulated kinase 1/2, p38, JNK, and Akt, and the transactivation of the epidermal growth factor receptor, pharmacological and molecular approaches demonstrated that only activation of ERK1, in addition to the CCAAT/enhancer-binding protein β transcription factor, is involved in transcriptional upregulation of SphK1 by LPA. Our data implicate ERK1 as an important mediator of LPA signaling leading to upregulation of SphK1 and point to SphK1 and sphingosine-1-phosphate production as potential therapeutic targets in gastric cancer.
authors.affiliation: Department of Biochemistry and Molecular Biology, Virginia Commonwealth University School of Medicine, Richmond, VA 23298-0614, USA.
authors.forename: Subramaniam
authors.initials: S
authors.lastname: Ramachandran
authors.forename: Dai
authors.initials: D
authors.lastname: Shida
authors.forename: Masayuki
authors.initials: M
authors.lastname: Nagahashi
authors.forename: Xianjun
authors.initials: X
authors.lastname: Fang
authors.forename: Sheldon
authors.initials: S
authors.lastname: Milstien
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Takabe
authors.forename: Sarah
authors.initials: S
authors.lastname: Spiegel
mesh_terms: D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008246:Lysophospholipids / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D015854:Up-Regulation; D000099157:Sphingosine Kinase
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; D008246:Lysophospholipids; D048052:Mitogen-Activated Protein Kinase 3; D017853:Phosphotransferases (Alcohol Group Acceptor); D047428:Protein Kinase Inhibitors; D000099157:Sphingosine Kinase; C545012:CEBPB protein, human; C032881:lysophosphatidic acid
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