• Open Access

The Wnt secretion protein Evi/Gpr177 promotes glioma tumourigenesis

Authors

  • Iris Augustin,

    Corresponding author
    1. German Cancer Research Center (DKFZ), Division of Signaling and Functional Genomics and Heidelberg University, Faculty of Medicine Mannheim, Department of Cell and Molecular Biology, Heidelberg, Germany
    • Iris Augustin, Tel: +49 6221 421955; Fax: +49 6221 421959

      Michael Boutros, Tel: +49 6221 421950; Fax: +49 2621 421959

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  • Violaine Goidts,

    1. German Cancer Research Center (DKFZ), Division of Molecular Genetics, Heidelberg, Germany
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  • Angelika Bongers,

    1. German Cancer Research Center (DKFZ), Division of Signaling and Functional Genomics and Heidelberg University, Faculty of Medicine Mannheim, Department of Cell and Molecular Biology, Heidelberg, Germany
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  • Grainne Kerr,

    1. German Cancer Research Center (DKFZ), Division of Signaling and Functional Genomics and Heidelberg University, Faculty of Medicine Mannheim, Department of Cell and Molecular Biology, Heidelberg, Germany
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  • Gordon Vollert,

    1. German Cancer Research Center (DKFZ), Division of Signaling and Functional Genomics and Heidelberg University, Faculty of Medicine Mannheim, Department of Cell and Molecular Biology, Heidelberg, Germany
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  • Bernhard Radlwimmer,

    1. German Cancer Research Center (DKFZ), Division of Molecular Genetics, Heidelberg, Germany
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  • Christian Hartmann,

    1. German Cancer Research Center (DKFZ), Clinical Cooperation Unit Neuropathology and Department of Neuropathology, Heidelberg University, Heidelberg, Germany
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  • Christel Herold-Mende,

    1. Division of Neurosurgical Research, Department of Neurosurgery, Heidelberg University, Heidelberg, Germany
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  • Guido Reifenberger,

    1. Department of Neuropathology, Heinrich-Heine-University, Düsseldorf, Germany
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  • Andreas von Deimling,

    1. German Cancer Research Center (DKFZ), Clinical Cooperation Unit Neuropathology and Department of Neuropathology, Heidelberg University, Heidelberg, Germany
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  • Michael Boutros

    Corresponding author
    1. German Cancer Research Center (DKFZ), Division of Signaling and Functional Genomics and Heidelberg University, Faculty of Medicine Mannheim, Department of Cell and Molecular Biology, Heidelberg, Germany
    • Iris Augustin, Tel: +49 6221 421955; Fax: +49 6221 421959

      Michael Boutros, Tel: +49 6221 421950; Fax: +49 2621 421959

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Abstract

Malignant astrocytomas are highly aggressive brain tumours with poor prognosis. While a number of structural genomic changes and dysregulation of signalling pathways in gliomas have been described, the identification of biomarkers and druggable targets remains an important task for novel diagnostic and therapeutic approaches. Here, we show that the Wnt-specific secretory protein Evi (also known as GPR177/Wntless/Sprinter) is overexpressed in astrocytic gliomas. Evi/Wls is a core Wnt signalling component and a specific regulator of pan-Wnt protein secretion, affecting both canonical and non-canonical signalling. We demonstrate that its depletion in glioma and glioma-derived stem-like cells led to decreased cell proliferation and apoptosis. Furthermore, Evi/Wls silencing in glioma cells reduced cell migration and the capacity to form tumours in vivo. We further show that Evi/Wls overexpression is sufficient to promote downstream Wnt signalling. Taken together, our study identifies Evi/Wls as an essential regulator of glioma tumourigenesis, identifying a pathway-specific protein trafficking factor as an oncogene and offering novel therapeutic options to interfere with the aberrant regulation of growth factors at the site of production.

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