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Sphingosine‐1‐phosphate (S1P) Signaling for Breast Cell Invasion
Author(s) -
Moon Aree,
Kim EunSook,
Kim JongSook,
Kim Sang Geon,
Hwang Sejin,
Lee Chang Ho
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.598.2
Subject(s) - sphingosine kinase 1 , sphingosine 1 phosphate , microbiology and biotechnology , sphingosine , protein kinase b , biology , sphingosine kinase , signal transduction , lipid signaling , g protein coupled receptor , kinase , downregulation and upregulation , pi3k/akt/mtor pathway , cancer research , inflammation , receptor , immunology , biochemistry , gene
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 Gαq 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 eterotrimeric Gαq subunit. Activation of phospholipase C‐β 4 and intracellular Ca 2+ 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 Gαq in MCF10A cells, thus providing a molecular basis for the crucial role of S1P in promoting breast cell invasion.