期刊
FEBS LETTERS
卷 584, 期 18, 页码 4077-4082出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.febslet.2010.08.035
关键词
Lysophosphatidic acid; Sphingosine kinase; Gastric cancer; Proliferation
资金
- National Institutes of Health [R37GM043880, R01CA61774]
- BIRCWH [K12HD055881]
- Susan G. Komen for the Cure [KG090510, RO1CA102196]
- SUMITOMO Life Social Welfare Services Foundation
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 beta 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. (c) 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
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