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Neurotrophin-induced melanoma cell migration is mediated through the actin-bundling protein fascin

Oncogene volume 22, pages 3616–3623 (2003)Cite this article

Abstract

Expression of the p75 neurotrophin receptor (p75NTR) in primary melanomas is associated with deeply invasive lesions. In turn, there is expression of high levels of neurotrophins at the invasion front of normal tissue adjacent to brain metastases, thus implicating this growth factor–receptor system in melanoma tumorigenesis. The neurotrophins nerve growth factor (NGF) and neurotrophin-3 (NT-3) are potent chemotactic agents for human melanoma cells which express p75NTRin vitro. Here we show that the actin-bundling protein fascin specifically interacts with p75NTR in an NGF-dependent manner by co-immunoprecipitation and colocalization in melanoma cells that express the two proteins endogenously. In addition, expression of a fascin point mutant at the serine phosphorylation site (serine 39) regulating actin binding abrogates neurotrophin-induced migration. These results suggest a causal role for NGF-mediated dephosphorylation of serine 39 on fascin in mediating actin binding and subsequent melanoma cell migration.

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Acknowledgements

We thank Patrick Haslett for a critical reading of the manuscript, and Lee Cohen-Gould for assistance with microscopy. This work was supported by an award from the Robert Wood Johnson Foundation to T Shonukan.

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Authors and Affiliations

  1. Department of Medicine, Division of Hematology/Oncology, University of Miami School of Medicine, Miami, 33136, FL, USA

    T Shonukan

  2. Department of Medicine, Division of Hematology/Oncology, Weill Medical College of Cornell University, New York, 10021, NY, USA

    I Bagayogo & B Hempstead

  3. Department of Biochemistry and Molecular Biology, The University of Texas, MD Anderson Cancer Center, Houston, 77030, TX, USA

    PD McCrea

  4. Departments of Cell Biology, Molecular Neurobiology Program, Skirball Institute for Biomolecular Medicine, New York, 10016, NY, USA

    M Chao

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  1. T Shonukan
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  2. I Bagayogo
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  4. M Chao
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  5. B Hempstead
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Correspondence to T Shonukan.

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Shonukan, T., Bagayogo, I., McCrea, P. et al. Neurotrophin-induced melanoma cell migration is mediated through the actin-bundling protein fascin. Oncogene 22, 3616–3623 (2003). https://doi.org/10.1038/sj.onc.1206561

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