JNK mediates insulin-like growth factor binding protein 2/integrin α5-dependent glioma cell migration

  • Authors: Kanchana Natarajan Mendes, George K. Wang, Gregory N. Fuller, Wei Zhang
  • View Affiliations

  • Published online on: Thursday, July 1, 2010
  • Pages: 143-153
  • DOI: 10.3892/ijo_00000662

Abstract

We have previously shown that a molecular interaction between insulin-like growth factor binding protein 2 (IGFBP2) and integrin α5 is necessary for the enhancement of cell migration in IGFBP2-overexpressing gliomas. In the present study, we examined the mechanism through which the IGFBP2/integrin α5 interaction mediates enhanced glioma cell migration. Although both ERK and JNK MAP kinases were activated, JNK was specifically involved in IGFBP2-mediated migration as shown by inhibitor analysis of IGFBP2-overexpressing cells. Because gliomas are solid tumors that require contact with a surface (e.g., other cells, extracellular matrix) for migration, we used the extracellular matrix (ECM) protein fibronectin, which is the sole ligand of the α5β1 integrin receptor, to show that integrin α5 is an important mediator of JNK activation. In addition, we found the IGFBP2/integrin α5 pathway to be activated in a significantly shorter interval in cells seeded onto fibronectin-coated surfaces compared to cells seeded onto plastic alone. The activation of JNK was downstream of the IGFBP2/integrin α5 interaction, as shown by α5 knockdown experiments using IGFBP2-overexpressing cells. Based on these data we propose that the interaction between IGFBP2 and integrin α5 accelerates cell adhesion, and this, in turn, enhances JNK-mediated glioma cell migration.
Journal Cover

July 2010
Volume 37 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

2012 Impact Factor: 2.657
Ranked #31/196 Oncology
(total number of cites)

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APA
Mendes, K., Wang, G., Fuller, G., & Zhang, W. (2010). JNK mediates insulin-like growth factor binding protein 2/integrin α5-dependent glioma cell migration. International Journal of Oncology, 37(1), 143-153.
MLA
Mendes, Wang, Fuller, and Wei Zhang. "JNK mediates insulin-like growth factor binding protein 2/integrin α5-dependent glioma cell migration." International Journal of Oncology International Journal of Oncology 37.1 (2010): 143-153.
Chicago
Mendes, Wang, Fuller, and Wei Zhang. "JNK mediates insulin-like growth factor binding protein 2/integrin α5-dependent glioma cell migration." International Journal of Oncology International Journal of Oncology 37 no. 1 (2010): 143-153.