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The Wnt secretion protein Evi/Gpr177 promotes glioma tumourigenesis.

Augustin I, Goidts V, Bongers A, Kerr G, Vollert G, Radlwimmer B, Hartmann C, Herold-Mende C, Reifenberger G, von Deimling A, Boutros M - EMBO Mol Med (2011)

Bottom Line: Malignant astrocytomas are highly aggressive brain tumours with poor prognosis.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 further show that Evi/Wls overexpression is sufficient to promote downstream Wnt signalling.

View Article: PubMed Central - PubMed

Affiliation: 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. i.augustin@dkfz.de

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Depletion of Evi induces apoptosis in glioblastoma-derived cancer stem-like cellsNeurosphere shape and size was disturbed after Evi silencing. Scale bar: 100 µm.Reduction in cell number compared to control transfected spheres 7 days after infection (**p < 0.01; ***p < 0.001).Lentiviral shRNA silencing of Evi expression in NCH421k and NCH644 cells led to an increase in the sub-G1 fraction (*p < 0.05; **p < 0.01).Representative graphs of cell cycle distribution. Data are expressed as mean ± SD of three-independent experiments.
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fig04: Depletion of Evi induces apoptosis in glioblastoma-derived cancer stem-like cellsNeurosphere shape and size was disturbed after Evi silencing. Scale bar: 100 µm.Reduction in cell number compared to control transfected spheres 7 days after infection (**p < 0.01; ***p < 0.001).Lentiviral shRNA silencing of Evi expression in NCH421k and NCH644 cells led to an increase in the sub-G1 fraction (*p < 0.05; **p < 0.01).Representative graphs of cell cycle distribution. Data are expressed as mean ± SD of three-independent experiments.

Mentions: Light microscopic analysis of SLGC spheres transduced with Evi shRNA versus control shRNA revealed strong morphological differences: Evi silenced spheres were significantly smaller and lost their packed condensed morphology compared to control spheres (Fig 4A and Fig S4 of Supporting information). Moreover, the amount of viable cells was significantly reduced in Evi depleted spheroid cultures (Fig 4B). Further analysis of apoptotic cells after Evi shRNA transduction revealed an increase in apoptosis as demonstrated by a significant rise in the sub-G1 fraction with no significant changes in cell cycle distribution (Fig 4C and D). These experiments demonstrate that Evi is required for cell survival in primary patient-derived glioblastoma cells.


The Wnt secretion protein Evi/Gpr177 promotes glioma tumourigenesis.

Augustin I, Goidts V, Bongers A, Kerr G, Vollert G, Radlwimmer B, Hartmann C, Herold-Mende C, Reifenberger G, von Deimling A, Boutros M - EMBO Mol Med (2011)

Depletion of Evi induces apoptosis in glioblastoma-derived cancer stem-like cellsNeurosphere shape and size was disturbed after Evi silencing. Scale bar: 100 µm.Reduction in cell number compared to control transfected spheres 7 days after infection (**p < 0.01; ***p < 0.001).Lentiviral shRNA silencing of Evi expression in NCH421k and NCH644 cells led to an increase in the sub-G1 fraction (*p < 0.05; **p < 0.01).Representative graphs of cell cycle distribution. Data are expressed as mean ± SD of three-independent experiments.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3306557&req=5

fig04: Depletion of Evi induces apoptosis in glioblastoma-derived cancer stem-like cellsNeurosphere shape and size was disturbed after Evi silencing. Scale bar: 100 µm.Reduction in cell number compared to control transfected spheres 7 days after infection (**p < 0.01; ***p < 0.001).Lentiviral shRNA silencing of Evi expression in NCH421k and NCH644 cells led to an increase in the sub-G1 fraction (*p < 0.05; **p < 0.01).Representative graphs of cell cycle distribution. Data are expressed as mean ± SD of three-independent experiments.
Mentions: Light microscopic analysis of SLGC spheres transduced with Evi shRNA versus control shRNA revealed strong morphological differences: Evi silenced spheres were significantly smaller and lost their packed condensed morphology compared to control spheres (Fig 4A and Fig S4 of Supporting information). Moreover, the amount of viable cells was significantly reduced in Evi depleted spheroid cultures (Fig 4B). Further analysis of apoptotic cells after Evi shRNA transduction revealed an increase in apoptosis as demonstrated by a significant rise in the sub-G1 fraction with no significant changes in cell cycle distribution (Fig 4C and D). These experiments demonstrate that Evi is required for cell survival in primary patient-derived glioblastoma cells.

Bottom Line: Malignant astrocytomas are highly aggressive brain tumours with poor prognosis.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 further show that Evi/Wls overexpression is sufficient to promote downstream Wnt signalling.

View Article: PubMed Central - PubMed

Affiliation: 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. i.augustin@dkfz.de

Show MeSH
Related in: MedlinePlus