The Wnt secretion protein Evi/Gpr177 promotes glioma tumourigenesis

被引：81

作者：

Augustin, Iris ^{[1
,2
]}

Goidts, Violaine ^{[3
]}

Bongers, Angelika ^{[1
,2
]}

Kerr, Grainne ^{[1
,2
]}

Vollert, Gordon ^{[1
,2
]}

Radlwimmer, Bernhard ^{[3
]}

Hartmann, Christian ^{[4
,5
]}

Herold-Mende, Christel ^{[6
]}

Reifenberger, Guido ^{[7
]}

von Deimling, Andreas ^{[4
,5
]}

Boutros, Michael ^{[1
,2
]}

机构：

[1] German Canc Res Ctr, Div Signaling & Funct Genom, Heidelberg, Germany

[2] Heidelberg Univ, Fac Med Mannheim, Dept Cell & Mol Biol, Heidelberg, Germany

[3] German Canc Res Ctr, Div Mol Genet, Heidelberg, Germany

[4] German Canc Res Ctr, Clin Cooperat Unit Neuropathol, Heidelberg, Germany

[5] Heidelberg Univ, Dept Neuropathol, Heidelberg, Germany

[6] Heidelberg Univ, Div Neurosurg Res, Dept Neurosurg, Heidelberg, Germany

[7] Univ Dusseldorf, Dept Neuropathol, D-40225 Dusseldorf, Germany

来源：

EMBO MOLECULAR MEDICINE | 2012年 / 4卷 / 01期

关键词：

cancer research; glioma; RNAi; Wnt secretion; Wnt signalling; PLANAR CELL POLARITY; SIGNALING PATHWAY; STEM-CELLS; EXPRESSION; PROLIFERATION; ACTIVATION; STAT3; IL-6; INFLAMMATION; INHIBITION;

D O I：

10.1002/emmm.201100186

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

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.

引用

页码：38 / 51

页数：14

共 62 条

[1] Differential recruitment of Dishevelled provides signaling specificity in the planar cell polarity and Wingless signaling pathways [J].