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

Cancer Lett. 2012 Dec 1;325(1):42-53. doi: 10.1016/j.canlet.2012.05.024. Epub 2012 May 28.

Authors

Ulf D Kahlert¹, 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

Affiliation

¹ Division of Stereotactic Neurosurgery, Department of General Neurosurgery, University Medical Center Freiburg, Freiburg, Germany.

PMID: 22652173
DOI: 10.1016/j.canlet.2012.05.024

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

AC133 Antigen
Antigens, CD / genetics
Antigens, CD / metabolism
Cell Differentiation / genetics
Cell Growth Processes / genetics
Cell Line, Tumor
Cell Movement / genetics
Cell Movement / physiology*
Epithelial-Mesenchymal Transition*
Glioblastoma / genetics
Glioblastoma / metabolism*
Glioblastoma / pathology*
Glycoproteins / genetics
Glycoproteins / metabolism
HEK293 Cells
Homeodomain Proteins / genetics
Homeodomain Proteins / metabolism*
Humans
Immunohistochemistry
Intercellular Signaling Peptides and Proteins / genetics
Intercellular Signaling Peptides and Proteins / metabolism
Neoplasm Invasiveness
Neoplastic Stem Cells / metabolism
Neoplastic Stem Cells / pathology
Peptides / genetics
Peptides / metabolism
Signal Transduction
Transcription Factors / genetics
Transcription Factors / metabolism*
Wnt Proteins / genetics
Wnt Proteins / metabolism
Wnt Signaling Pathway*
Zinc Finger E-box-Binding Homeobox 1
beta Catenin / genetics
beta Catenin / metabolism

Substances

AC133 Antigen
Antigens, CD
DKK1 protein, human
Glycoproteins
Homeodomain Proteins
Intercellular Signaling Peptides and Proteins
Peptides
Transcription Factors
Wnt Proteins
ZEB1 protein, human
Zinc Finger E-box-Binding Homeobox 1
beta Catenin