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Sphingosine 1-phosphate regulates matrix metalloproteinase-9 expression and breast cell invasion through S1P3-Gaq coupling

Title
Sphingosine 1-phosphate regulates matrix metalloproteinase-9 expression and breast cell invasion through S1P3-Gaq coupling
Author
이창호
Keywords
S1P; Breast cell invasion; MMP-9
Issue Date
2011-07
Publisher
COMPANY OF BIOLOGISTS LTD
Citation
Journal of Cell Science, 2011, 124(13), P.2220-2230
Abstract
Recent evidence suggests that inflammation is involved in malignant progression of breast cancer. Sphingosine 1-phosphate (S1P), acting on the G-protein-coupled receptors, is known as a potent inflammatory mediator. In this study, the effect of the inflammatory lipid S1P on the regulation of invasive/migratory phenotypes of MCF10A human breast epithelial cells was investigated to elucidate a causal relationship between inflammation and the control of invasiveness of breast cells. We show that S1P causes induction of matrix metalloproteinase-9 (MMP-9) in vitro and in vivo, and thus enhances invasion and migration. We also show that fos plays a crucial role in the transcriptional activation of MMP-9 by S1P. In addition, activation of extracellular-signal-regulated kinases 1 and 2 (ERK1/2), p38 and alpha serine/threonine-protein kinase (Akt) are involved in the process of S1P-mediated induction of MMP-9 expression and invasion. Activation of the S1P receptor S1P(3) and G(alpha q) are required for S1P-induced invasive/migratory responses, suggesting that the enhancement of S1P-mediated invasiveness is triggered by the specific coupling of S1P(3) to the heterotrimeric G(alpha q) subunit. Activation of phospholipase C-beta(4) and intracellular Ca2+ release are required for S1P-induced MMP-9 upregulation. Taken together, this study demonstrated that S1P regulates MMP-9 induction and invasiveness through coupling of S1P(3) and G(alpha q) in MCF10A cells, thus providing a molecular basis for the crucial role of S1P in promoting breast cell invasion.
URI
http://jcs.biologists.org/content/124/13/2220
ISSN
0021-9533
DOI
10.1242/jcs.076794
Appears in Collections:
COLLEGE OF MEDICINE[S](의과대학) > MEDICINE(의학과) > Articles
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