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

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)42-53
Number of pages12
JournalCancer Letters
Volume325
Issue number1
DOIs
StatePublished - Dec 1 2012

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Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

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