Osteopontin stimulates melanoma growth and lung metastasis through NIK/MEKK1-dependent MMP-9 activation pathways

  • Authors:
    • Hema Rangaswami
    • Gopal C. Kundu
  • View Affiliations

  • Published online on: October 1, 2007     https://doi.org/10.3892/or.18.4.909
  • Pages: 909-915
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Abstract

We examined the role of osteopontin (OPN) in NIK- and MEKK1-dependent MMP-9 activation, melanoma growth and lung metastasis and its clinical significance in malignant melanoma. Here we report that OPN induces αvβ3 integrin-mediated MEKK1-dependent JNK1 phosphorylation. OPN stimulates NIK- or JNK1-dependent c-Jun expression. In contrast, OPN induces MEKK1-dependent JNK1 activation that leads to downregulation of ERK1/2 activation. OPN triggers NIK- and MEKK1-dependent AP-1 activation whereas NIK-dependent AP-1 activation is independent of JNK1 that leads to pro-MMP-9 activation. In vivo studies indicate that the levels of pNIK and MMP-9 are significantly higher in the OPN-induced primary tumor and metastasized lung compared to control. Clinical data revealed that the enhanced level of OPN and pNIK expression in the skin biopsies correlates with Clark's level and Breslow thickness. Altogether, OPN regulates negative cross-talk between NIK/ERK and MEKK1/JNK1 pathways that controls melanoma progression.

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October 2007
Volume 18 Issue 4

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Rangaswami H and Kundu GC: Osteopontin stimulates melanoma growth and lung metastasis through NIK/MEKK1-dependent MMP-9 activation pathways. Oncol Rep 18: 909-915, 2007.
APA
Rangaswami, H., & Kundu, G.C. (2007). Osteopontin stimulates melanoma growth and lung metastasis through NIK/MEKK1-dependent MMP-9 activation pathways. Oncology Reports, 18, 909-915. https://doi.org/10.3892/or.18.4.909
MLA
Rangaswami, H., Kundu, G. C."Osteopontin stimulates melanoma growth and lung metastasis through NIK/MEKK1-dependent MMP-9 activation pathways". Oncology Reports 18.4 (2007): 909-915.
Chicago
Rangaswami, H., Kundu, G. C."Osteopontin stimulates melanoma growth and lung metastasis through NIK/MEKK1-dependent MMP-9 activation pathways". Oncology Reports 18, no. 4 (2007): 909-915. https://doi.org/10.3892/or.18.4.909