Sphingosine 1-phosphate regulates matrix metalloproteinase-9 expression and breast cell invasion through S1P(3)-G(alpha q) coupling
- Authors
- Kim, Eun-Sook; Kim, Jong-Sook; Kim, Sang Geon; Hwang, Sejin; Lee, Chang Ho; Moon, Aree
- Issue Date
- Jul-2011
- Publisher
- COMPANY BIOLOGISTS LTD
- Keywords
- S1P; Breast cell invasion; MMP-9
- Citation
- JOURNAL OF CELL SCIENCE, v.124, no.13, pp.2220 - 2230
- Indexed
- SCIE
SCOPUS
- Journal Title
- JOURNAL OF CELL SCIENCE
- Volume
- 124
- Number
- 13
- Start Page
- 2220
- End Page
- 2230
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/168048
- DOI
- 10.1242/jcs.076794
- ISSN
- 0021-9533
- 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 S1P₃ 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 S1P₃ to the heterotrimeric G(alpha q) subunit. Activation of phospholipase C-beta₄ 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 S1P₃ and G(alpha q) in MCF10A cells, thus providing a molecular basis for the crucial role of S1P in promoting breast cell invasion.
- Files in This Item
- There are no files associated with this item.
- Appears in
Collections - 서울 의과대학 > 서울 약리학교실 > 1. Journal Articles
- 서울 의과대학 > 서울 해부·세포생물학교실 > 1. Journal Articles
![qrcode](https://api.qrserver.com/v1/create-qr-code/?size=55x55&data=https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/168048)
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.