Activation of canonical WNT/β-catenin signaling enhances in vitro motility of glioblastoma cells by activation of ZEB1 and other activators of epithelial-to-mesenchymal transition

Ulf D. Kahlert; Donata Maciaczyk; Soroush Doostkam; Brent A. Orr; Brian Simons; Tomasz Bogiel; Thomas Reithmeier; Marco Prinz; Jörg Schubert; Gabriele Niedermann; Thomas Brabletz; Charles G. Eberhart; Guido Nikkhah; Jaroslaw Maciaczyk

doi:10.1016/j.canlet.2012.05.024

Activation of canonical WNT/β-catenin signaling enhances in vitro motility of glioblastoma cells by activation of ZEB1 and other activators of epithelial-to-mesenchymal transition

Ulf D. Kahlert, Donata Maciaczyk, Soroush Doostkam, Brent A. Orr, Brian Simons, Tomasz Bogiel, Thomas Reithmeier, Marco Prinz, Jörg Schubert, Gabriele Niedermann, Thomas Brabletz, Charles G. Eberhart, Guido Nikkhah, Jaroslaw Maciaczyk

School of Medicine

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140 Scopus citations

Abstract

Here we show that activation of the canonical WNT/β-catenin pathway increases the expression of stem cell genes and promotes the migratory and invasive capacity of glioblastoma. Modulation of WNT signaling alters the expression of epithelial-to-mesenchymal transition activators, suggesting a role of this process in the regulation of glioma motility. Using immunohistochemistry in patient-derived glioblastoma samples we showed higher numbers of cells with intranuclear signal for β-catenin in the infiltrating edge of tumor compared to central tumor parenchyma. These findings suggest that canonical WNT/β-catenin pathway is a critical regulator of GBM invasion and may represent a potential therapeutic target.

Original language	English (US)
Pages (from-to)	42-53
Number of pages	12
Journal	Cancer Letters
Volume	325
Issue number	1
DOIs	https://doi.org/10.1016/j.canlet.2012.05.024
State	Published - Dec 1 2012

Keywords

Epithelial-to-mesenchymal transition (EMT)
Glioblastoma
Invasion
ZEB1
β-Catenin

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1016/j.canlet.2012.05.024

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Kahlert, U. D., Maciaczyk, D., Doostkam, S., Orr, B. A., Simons, B., Bogiel, T., Reithmeier, T., Prinz, M., Schubert, J., Niedermann, G., Brabletz, T., Eberhart, C. G., Nikkhah, G., & Maciaczyk, J. (2012). Activation of canonical WNT/β-catenin signaling enhances in vitro motility of glioblastoma cells by activation of ZEB1 and other activators of epithelial-to-mesenchymal transition. Cancer Letters, 325(1), 42-53. https://doi.org/10.1016/j.canlet.2012.05.024

Activation of canonical WNT/β-catenin signaling enhances in vitro motility of glioblastoma cells by activation of ZEB1 and other activators of epithelial-to-mesenchymal transition. / Kahlert, Ulf D.; Maciaczyk, Donata; Doostkam, Soroush et al.
In: Cancer Letters, Vol. 325, No. 1, 01.12.2012, p. 42-53.

Research output: Contribution to journal › Article › peer-review

Kahlert, UD, Maciaczyk, D, Doostkam, S, Orr, BA, Simons, B, Bogiel, T, Reithmeier, T, Prinz, M, Schubert, J, Niedermann, G, Brabletz, T, Eberhart, CG, Nikkhah, G & Maciaczyk, J 2012, 'Activation of canonical WNT/β-catenin signaling enhances in vitro motility of glioblastoma cells by activation of ZEB1 and other activators of epithelial-to-mesenchymal transition', Cancer Letters, vol. 325, no. 1, pp. 42-53. https://doi.org/10.1016/j.canlet.2012.05.024

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abstract = "Here we show that activation of the canonical WNT/β-catenin pathway increases the expression of stem cell genes and promotes the migratory and invasive capacity of glioblastoma. Modulation of WNT signaling alters the expression of epithelial-to-mesenchymal transition activators, suggesting a role of this process in the regulation of glioma motility. Using immunohistochemistry in patient-derived glioblastoma samples we showed higher numbers of cells with intranuclear signal for β-catenin in the infiltrating edge of tumor compared to central tumor parenchyma. These findings suggest that canonical WNT/β-catenin pathway is a critical regulator of GBM invasion and may represent a potential therapeutic target.",

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note = "Funding Information: This work was supported by the Comprehensive Cancer Center Freiburg Seeding Grant (Deutsche Krebshilfe) awarded to J. Maciaczyk and G. Nikkhah. ",

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AU - Brabletz, Thomas

AU - Eberhart, Charles G.

AU - Nikkhah, Guido

AU - Maciaczyk, Jaroslaw

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AB - Here we show that activation of the canonical WNT/β-catenin pathway increases the expression of stem cell genes and promotes the migratory and invasive capacity of glioblastoma. Modulation of WNT signaling alters the expression of epithelial-to-mesenchymal transition activators, suggesting a role of this process in the regulation of glioma motility. Using immunohistochemistry in patient-derived glioblastoma samples we showed higher numbers of cells with intranuclear signal for β-catenin in the infiltrating edge of tumor compared to central tumor parenchyma. These findings suggest that canonical WNT/β-catenin pathway is a critical regulator of GBM invasion and may represent a potential therapeutic target.

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Activation of canonical WNT/β-catenin signaling enhances in vitro motility of glioblastoma cells by activation of ZEB1 and other activators of epithelial-to-mesenchymal transition

Abstract

Keywords

ASJC Scopus subject areas

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