Original Research Article
Endothelin-1 promotes MMP-13 production and migration in human chondrosarcoma cells through FAK/PI3K/Akt/mTOR pathways
Article first published online: 23 APR 2012
Copyright © 2011 Wiley Periodicals, Inc.
Journal of Cellular Physiology
Volume 227, Issue 8, pages 3016–3026, August 2012
How to Cite
Wu, M. H., Lo, J.-F., Kuo, C.-H., Lin, J. A., Lin, Y.-M., Chen, L.-M., Tsai, F.-J., Tsai, C.-H., Huang, C.-Y. and Tang, C.-H. (2012), Endothelin-1 promotes MMP-13 production and migration in human chondrosarcoma cells through FAK/PI3K/Akt/mTOR pathways. J. Cell. Physiol., 227: 3016–3026. doi: 10.1002/jcp.23043
- Issue published online: 23 APR 2012
- Article first published online: 23 APR 2012
- Accepted manuscript online: 29 SEP 2011 07:30AM EST
- Manuscript Accepted: 26 SEP 2011
- Manuscript Received: 15 FEB 2011
- National Science Council of Taiwan. Grant Number: NSC99-2320-B-039-003-MY3
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.