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  • Original Paper
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Melanoma cell migration to type IV collagen requires activation of NF-κB

Oncogene volume 22, pages 98–108 (2003)Cite this article

Abstract

Chemotaxis is the consequence of environmental factors engaging their receptors to initiate signaling cascades. However, the biochemical mechanisms controlling this phenomenon are not clear. We employed an in vitro modified Boyden 48-well chemotaxis migration system to characterize the role of signal transducers in type IV collagen (CIV) induced A2058 human melanoma cell migration. Using specific pharmacological inhibitors and a series of dominant-negative and constitutively active signaling proteins, we show that Ras and Rac GTPases, PI-3K, and PKC participate in cell migration mediated by β1 integrins. Collagen also induces a time- dependent degradation of IκB-α and an increase in nuclear translocation of NF-κB which is dependent on PKC pathway. More importantly, collagen-stimulated melanoma cell migration directly correlated with an increase in NF-κB transactivation. Furthermore, CIV induced an increase in β1 integrin mRNA levels. Specific NF-κB inhibitors Helenalin and SN-50 inhibited melanoma cell migration to collagen, indicating a novel requirement for NF-κB transactivation in cell chemotaxis mediated by β1 integrin signals. These results describe signal transduction events that are initiated by type IV collagen through β1 integrins and demonstrate an important role for NF-κB in regulating melanoma chemotaxis.

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Acknowledgements

The authors thank Dr MA Schwartz (The Scripps Research Institute), Dr K Calame (Columbia University), Dr A August, Dr P Correll, and Dr JM Tarbell (Penn State University) for their generous gifts of cDNA constructs and pertinent reagents. The authors also thank Dr A August for his critical reading, helpful comments and discussions. Technical assistance of Eileen S Lee, Julie A Cook (Penn State University), and Elaine L Kunze (Flowcytometry facility, Penn State University) are also appreciated. This work was supported by NIH-CA76434 (CD), and NIH-AI46261 (AJH).

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  1. Department of Bioengineering, 229 Hallowell, The Pennsylvania State University, University Park, 16802, PA, USA

    Louis Hodgson & Cheng Dong

  2. Department of Veterinary Science, 115 Henning, The Pennsylvania State University, University Park, 16802, PA, USA

    Andrew J Henderson

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  1. Louis Hodgson
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  2. Andrew J Henderson
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Correspondence to Cheng Dong.

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Hodgson, L., Henderson, A. & Dong, C. Melanoma cell migration to type IV collagen requires activation of NF-κB. Oncogene 22, 98–108 (2003). https://doi.org/10.1038/sj.onc.1206059

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