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Endothelin-1 promotes MMP-13 production and migration in human chondrosarcoma cells through FAK/PI3K/Akt/mTOR pathways
Tumor malignancy is associated with several cellular properties including proliferation and ability to metastasize. Endothelin‐1 (ET‐1) the most potent vasoconstrictor plays a crucial role in migration and metastasis of human cancer cells. We found that treatment of human chondrosarcoma (JJ012 cells...
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Published in: | Journal of cellular physiology 2012-08, Vol.227 (8), p.3016-3026 |
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Main Authors: | , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Tumor malignancy is associated with several cellular properties including proliferation and ability to metastasize. Endothelin‐1 (ET‐1) the most potent vasoconstrictor plays a crucial role in migration and metastasis of human cancer cells. We found that treatment of human chondrosarcoma (JJ012 cells) with ET‐1 increased migration and expression of matrix metalloproteinase (MMP)‐13. ET‐1‐mediated cell migration and MMP‐13 expression were reduced by pretreatment with inhibitors of focal adhesion kinase (FAK), phosphatidylinositol 3‐kinase (PI3K), Akt, and mammalian target of rapamycin (mTOR), as well as the NF‐κB inhibitor and the IκB protease inhibitor. In addition, ET‐1 treatment induced phosphorylation of FAK, PI3K, AKT, and mTOR, and resulted in increased NF‐κB‐luciferase activity that was inhibited by a specific inhibitor of PI3K, Akt, mTOR, and NF‐κB cascades. Taken together, these results suggest that ET‐1 activated FAK/PI3K/AKT/mTOR, which in turn activated IKKα/β and NF‐κB, resulting in increased MMP‐13 expression and migration in human chondrosarcoma cells. J. Cell. Physiol. 227: 3016–3026, 2012. © 2011 Wiley Periodicals, Inc. |
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ISSN: | 0021-9541 1097-4652 |
DOI: | 10.1002/jcp.23043 |