Sphingosine 1‐phosphate regulates matrix metalloproteinase‐9 expression and breast cell invasion through S1P3‐Gαq coupling
العنوان: | Sphingosine 1‐phosphate regulates matrix metalloproteinase‐9 expression and breast cell invasion through S1P3‐Gαq coupling |
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المؤلفون: | Aree Moon, Sejin Hwang, Eun-Sook Kim, Chang Ho Lee, Sang Geon Kim, Jong-Sook Kim |
المصدر: | The FASEB Journal. 26 |
بيانات النشر: | Wiley, 2012. |
سنة النشر: | 2012 |
مصطلحات موضوعية: | Sphingosine-1-phosphate receptor, Breast Neoplasms, Biochemistry, Cell Line, Mice, chemistry.chemical_compound, Cell Movement, Sphingosine, Heterotrimeric G protein, Genetics, Animals, Humans, Neoplasm Invasiveness, Breast, Sphingosine-1-phosphate, Protein kinase A, Protein kinase B, Molecular Biology, Cell invasion, biology, Chemistry, Matrix metalloproteinase 9, Cell Biology, Cell biology, Mice, Inbred C57BL, Coupling (electronics), Receptors, Lysosphingolipid, Oncogene Proteins v-fos, Matrix Metalloproteinase 9, Gq alpha subunit, biology.protein, GTP-Binding Protein alpha Subunits, Gq-G11, Female, lipids (amino acids, peptides, and proteins), Lysophospholipids, Signal transduction, Signal Transduction, Biotechnology |
الوصف: | 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 Gαq 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 Gαq subunit. Activation of phospholipase C-β4 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 Gαq in MCF10A cells, thus providing a molecular basis for the crucial role of S1P in promoting breast cell invasion. |
تدمد: | 1530-6860 0892-6638 |
الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::20526671a51fedbe9ab266ad0770d3aaTest https://doi.org/10.1096/fasebj.26.1_supplement.782.4Test |
حقوق: | OPEN |
رقم الانضمام: | edsair.doi.dedup.....20526671a51fedbe9ab266ad0770d3aa |
قاعدة البيانات: | OpenAIRE |
تدمد: | 15306860 08926638 |
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