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.
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.
Division of Stereotactic Neurosurgery, Department of General Neurosurgery, University Medical Center Freiburg, Freiburg, Germany.
Ulf D
UD
Kahlert
Donata
D
Maciaczyk
Soroush
S
Doostkam
Brent A
BA
Orr
Brian
B
Simons
Tomasz
T
Bogiel
Thomas
T
Reithmeier
Marco
M
Prinz
Jörg
J
Schubert
Gabriele
G
Niedermann
Thomas
T
Brabletz
Charles G
CG
Eberhart
Guido
G
Nikkhah
Jaroslaw
J
Maciaczyk
D000071916:AC133 Antigen; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D048708:Cell Growth Processes / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D058750:Epithelial-Mesenchymal Transition; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism; D060449:Wnt Signaling Pathway; D000071799:Zinc Finger E-box-Binding Homeobox 1; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
D000071916:AC133 Antigen; D015703:Antigens, CD; C501126:DKK1 protein, human; D006023:Glycoproteins; D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D014157:Transcription Factors; D051153:Wnt Proteins; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1; D051176:beta Catenin