Glial cell-derived neurotrophic factor increases migration of human chondrosarcoma cells via ERK and NF-κB pathways

Chen Ming Su, Dah Yuu Lu, Chin Jung Hsu, Hsien Te Chen, Chun Yin Huang, Wei Hung Yang, Yi Chang Su, Shu Ning Yang, Yi Chin Fong, Wen Pei Tseng, Chih Hsin Tang

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Abstract

Invasion of tumor cells is the primary cause of therapeutic failure in the treatment of malignant chondrosarcomas. Glial cell-derived neurotrophic factor (GDNF) 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 GDNF directed the migration and increased cell surface expression of αv and β3 integrin in human chondrosarcoma cells. Pretreated of JJ012 cells with MAPK kinase (MEK) inhibitors PD98059 or U0126 inhibited the GDNF-mediated migration and integrin expression. Stimulation of cells with GDNF increased the phosphorylation of MEK and extracellular signal-regulating kinase (ERK). In addition, NF-κB inhibitor (PDTC) or IκB protease inhibitor (TPCK) also inhibited GDNF-mediated cells migration and integrin up-regulation. Stimulation of cells withGDNFinduced IkB kinase (IKKκ/β) phosphorylation, IκB phosphorylation, p65 Ser536 phosphorylation, and κB-luciferase activity. Furthermore, the GDNF-mediated increasing of κB-luciferase activity was inhibited by PD98059, U0126, PDTC and TPCK or MEK, ERK, IKKα, and IKKβ mutants. Taken together, these results suggest that the GDNF acts through MEK/ERK, which in turn activates IKKα/β and NF-κB, resulting in the activations of αvβ3 integrin and contributing the migration of human chondrosarcoma cells.

Original languageEnglish
Pages (from-to)499-507
Number of pages9
JournalJournal of Cellular Physiology
Volume220
Issue number2
DOIs
Publication statusPublished - 2009 Aug 1

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All Science Journal Classification (ASJC) codes

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Su, C. M., Lu, D. Y., Hsu, C. J., Chen, H. T., Huang, C. Y., Yang, W. H., Su, Y. C., Yang, S. N., Fong, Y. C., Tseng, W. P., & Tang, C. H. (2009). Glial cell-derived neurotrophic factor increases migration of human chondrosarcoma cells via ERK and NF-κB pathways. Journal of Cellular Physiology, 220(2), 499-507. https://doi.org/10.1002/jcp.21802