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

Research output: Contribution to journalArticle

29 Citations (Scopus)

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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Chondrosarcoma
Nerve Growth Factors
Neuroglia
Phosphotransferases
Mitogen-Activated Protein Kinase Kinases
Phosphorylation
Integrins
Tosylphenylalanyl Chloromethyl Ketone
Cells
Luciferases
Cell Movement
Protease Inhibitors
Treatment Failure
Tumors
Adhesives
Chemical activation
Neoplasms
Up-Regulation
Molecules
Neoplasm Metastasis

All Science Journal Classification (ASJC) codes

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Su, Chen Ming ; Lu, Dah Yuu ; Hsu, Chin Jung ; Chen, Hsien Te ; Huang, Chun Yin ; Yang, Wei Hung ; Su, Yi Chang ; Yang, Shu Ning ; Fong, Yi Chin ; Tseng, Wen-Pei ; Tang, Chih Hsin. / Glial cell-derived neurotrophic factor increases migration of human chondrosarcoma cells via ERK and NF-κB pathways. In: Journal of Cellular Physiology. 2009 ; Vol. 220, No. 2. pp. 499-507.
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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.",
author = "Su, {Chen Ming} and Lu, {Dah Yuu} and Hsu, {Chin Jung} and Chen, {Hsien Te} and Huang, {Chun Yin} and Yang, {Wei Hung} and Su, {Yi Chang} and Yang, {Shu Ning} and Fong, {Yi Chin} and Wen-Pei Tseng and Tang, {Chih Hsin}",
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Su, CM, Lu, DY, Hsu, CJ, Chen, HT, Huang, CY, Yang, WH, Su, YC, Yang, SN, Fong, YC, Tseng, W-P & Tang, CH 2009, 'Glial cell-derived neurotrophic factor increases migration of human chondrosarcoma cells via ERK and NF-κB pathways', Journal of Cellular Physiology, vol. 220, no. 2, pp. 499-507. https://doi.org/10.1002/jcp.21802

Glial cell-derived neurotrophic factor increases migration of human chondrosarcoma cells via ERK and NF-κB pathways. / Su, Chen Ming; Lu, Dah Yuu; Hsu, Chin Jung; Chen, Hsien Te; Huang, Chun Yin; Yang, Wei Hung; Su, Yi Chang; Yang, Shu Ning; Fong, Yi Chin; Tseng, Wen-Pei; Tang, Chih Hsin.

In: Journal of Cellular Physiology, Vol. 220, No. 2, 01.08.2009, p. 499-507.

Research output: Contribution to journalArticle

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T1 - Glial cell-derived neurotrophic factor increases migration of human chondrosarcoma cells via ERK and NF-κB pathways

AU - Su, Chen Ming

AU - Lu, Dah Yuu

AU - Hsu, Chin Jung

AU - Chen, Hsien Te

AU - Huang, Chun Yin

AU - Yang, Wei Hung

AU - Su, Yi Chang

AU - Yang, Shu Ning

AU - Fong, Yi Chin

AU - Tseng, Wen-Pei

AU - Tang, Chih Hsin

PY - 2009/8/1

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N2 - 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.

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