摘要
Bone morphogenetic protein-2 (BMP-2), a member of transforming growth factor-β superfamily, plays a crucial role in migration and metastasis of human cancer cells. Integrins are the major adhesive molecules in mammalian cells. Here we found that BMP-2 directed the migration and increased cell surface and mRNA expression of β1 integrin in human chondrosarcoma cancer cells (JJ012). Pretreated of JJ012 cells with phosphatidylinositol 3-kinase inhibitor (PI3K; Ly294002) or Akt inhibitor inhibited the BMP-2-mediated migration and integrin expression. BMP-2 increased the phosphorylation of p85 subunit of PI3K and serine 473 of Akt. In addition, NF-κB inhibitor (PDTC) or IκB protease inhibitor (TPCK) also inhibited BMP-2-mediated cells migration and integrin upregulation. Stimulation of JJ012 cells with BMP-2 induced IκB kinase (IKKα/β) phosphorylation, IκB phosphorylation, p65 Ser536 phosphorylation, and κB-luciferase activity. Furthermore, the BMP-2-mediated increasing of IKKα/β phosphorylation, IκB phosphorylation, and p65 Ser536 phosphorylation were inhibited by Ly294002 and Akt inhibitor. Co-transfection with p85 and Akt mutants also reduced the BMP-2-induced κB-luciferase activity. Taken together, these results suggest that the BMP-2 acts through PI3K/Akt, which in turn activates IKKα/β and NF-κB, resulting in the activations of β1 integrin and contributing the migration of human chondrosarcoma cells.
原文 | 英語 |
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頁(從 - 到) | 846-855 |
頁數 | 10 |
期刊 | Journal of Cellular Physiology |
卷 | 217 |
發行號 | 3 |
DOIs | |
出版狀態 | 已發佈 - 12月 2008 |
對外發佈 | 是 |
ASJC Scopus subject areas
- 臨床生物化學
- 細胞生物學
- 生理學