Abstract
Abstract Tumor malignancy is associated with several features such as proliferation ability and frequency of metastasis. Endothelin-1 (ET-1), the most potent vasoconstrictor, and plays a crucial role in the migration and metastasis of human cancer cells. We found that treatment of human chondrosarcoma cells (JJ012 cells) with ET-1 increased migration activity and the expression of matrix metalloproteinase (MMP)-13. Pretreatment of cells with phosphatidylinositol 3-kinase (PI3K), AKT and mammalian Target of Rapamycin (mTOR) inhibitor reduced ET-1- mediated cell migration and MMP-13 expression. In addition, NF-kappaB inhibitor (PDTC) or IkappaB protease inhibitor (TPCK) also inhibited ET-1 -mediated cell migration and MMP-13 up-regulation. Stimulation of cell with ET-1 induced PI3K, AKT and mTOR phosphorylation. Furthermore, the ET-1-mediated increasing kappaB-luciferase activity was inhibited by the specific inhibitor of PI3K, Akt and NF-kB cascades. Taken together, these results suggest that the ET-1 activate PI3K/AKT/mTOR, which in turn activates IKKalpha/beta and NF-kappaB, resulting in the activations of MMP-13 and contributing the migration of human chondrosarcoma cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5272.
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