BMP-2 increases migration of human chondrosarcoma cells via PI3K/Akt pathway

Yi Chin Fong, Te Mao Li, Chi Ming Wu, Sheng Feng Hsu, Shung Te Kao, Ray Jade Chen, Cheng Chieh Lin, Shan Chi Liu, Chien Lin Wu, Chih Hsin Tang

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Abstract

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.

Original languageEnglish
Pages (from-to)846-855
Number of pages10
JournalJournal of Cellular Physiology
Volume217
Issue number3
DOIs
Publication statusPublished - Dec 2008
Externally publishedYes

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

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  • Cite this

    Fong, Y. C., Li, T. M., Wu, C. M., Hsu, S. F., Kao, S. T., Chen, R. J., Lin, C. C., Liu, S. C., Wu, C. L., & Tang, C. H. (2008). BMP-2 increases migration of human chondrosarcoma cells via PI3K/Akt pathway. Journal of Cellular Physiology, 217(3), 846-855. https://doi.org/10.1002/jcp.21568