| First Author | Kim ES | Year | 2011 |
| Journal | J Cell Sci | Volume | 124 |
| Issue | Pt 13 | Pages | 2220-30 |
| PubMed ID | 21652634 | Mgi Jnum | J:183054 |
| Mgi Id | MGI:5317391 | Doi | 10.1242/jcs.076794 |
| Citation | Kim ES, et al. (2011) Sphingosine 1-phosphate regulates matrix metalloproteinase-9 expression and breast cell invasion through S1P3-Galphaq coupling. J Cell Sci 124(Pt 13):2220-30 |
| abstractText | 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 and G(alphaq) are required for S1P-induced invasive/migratory responses, suggesting that the enhancement of S1P-mediated invasiveness is triggered by the specific coupling of S1P to the heterotrimeric G(alphaq) subunit. Activation of phospholipase C-beta 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 and G(alphaq) in MCF10A cells, thus providing a molecular basis for the crucial role of S1P in promoting breast cell invasion. |
