Endothelin-1 promotes MMP-13 production and migration in human chondrosarcoma cells through FAK/PI3K/Akt/mTOR pathways.

Abstract

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.

DOI: 10.1002/jcp.23043
0200400201220132014201520162017
Citations per Year

719 Citations

Semantic Scholar estimates that this publication has 719 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@article{Wu2012Endothelin1PM, title={Endothelin-1 promotes MMP-13 production and migration in human chondrosarcoma cells through FAK/PI3K/Akt/mTOR pathways.}, author={Min Wu and Jeng-Fan Lo and Chia-Hua Kuo and James A. Lin and Yueh-min Lin and Li-mien Chen and Fuu-Jen Tsai and Chang-Hai Tsai and Chih-Yang Huang and Chih-Hsin Tang}, journal={Journal of cellular physiology}, year={2012}, volume={227 8}, pages={3016-26} }