The Wnt secretion protein Evi/Gpr177 promotes glioma tumourigenesis

EMBO Molecular Medicine

Iris Augustin³  Violaine Goidts²  Angelika Bongers⁶  Grainne Kerr⁶  Gordon Vollert⁶  Bernhard Radlwimmer²  Christian Hartmann⁵  Christel Herold-Mende¹  Guido Reifenberger⁴  Andreas von Deimling⁵ 

[1] Division of Neurosurgical Research, Department of Neurosurgery, Heidelberg University, Heidelberg, Germany;German Cancer Research Center (DKFZ), Division of Molecular Genetics, Heidelberg, Germany;E-mail address: 关键词: cancer research;    glioma;    RNAi;    Wnt secretion;    Wnt signalling;   

DOI  :  10.1002/emmm.201100186

来源: Wiley

【 摘 要 】

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.

【 授权许可】

Unknown   
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