LGR5 is a marker of poor prognosis in glioblastoma and is required for survival of brain cancer stem-like cells.
In various types of cancers including glioblastoma, accumulating evidence show the existence of cancer stem-like cells (CSCs), characterized by stem cell marker expression, capability of differentiation and self-renewal, and high potential for tumor propagation in vivo. LGR5, whose expression is positively regulated by the Wnt signaling pathway, is a stem cell marker in intestinal mucosa and hair follicle in the skin. As Wnt signaling is also involved in brain development, the function of LGR5 in the maintenance of brain CSCs is to be assessed. Our study showed that the LGR5 transcript level was increased in CSCs. Co-immunofluorescence staining demonstrated the co-localization of CD133- and LGR5-positive cells in glioblastoma tissue sections. Functionally, silencing of LGR5 by lentiviral shRNA-mediated knockdown induced apoptosis in brain CSCs. Moreover, LGR5 depletion led to a downregulation of L1 cell adhesion molecule expression. In line with an important function in glioma tumorigenesis, LGR5 expression increased with glioma progression and correlated with an adverse outcome. Our findings suggest that LGR5 plays a role in maintenance and/or survival of brain CSCs.
Division of Molecular Genetics, German Cancer Research Center, Heidelberg, Germany.
Susumu
S
Nakata
Benito
B
Campos
Josephine
J
Bageritz
Justo Lorenzo
JL
Bermejo
Natalia
N
Becker
Felix
F
Engel
Till
T
Acker
Stefan
S
Momma
Christel
C
Herold-Mende
Peter
P
Lichter
Bernhard
B
Radlwimmer
Violaine
V
Goidts
D000071916:AC133 Antigen; D015703:Antigens, CD / Q000378:metabolism; D017209:Apoptosis; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000473:pathology*; D002454:Cell Differentiation / Q000235:genetics; D002470:Cell Survival; D002478:Cells, Cultured; D015972:Gene Expression Regulation, Neoplastic; D005822:Genetic Vectors / Q000502:physiology; D005909:Glioblastoma / Q000175:diagnosis* / Q000473:pathology*; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D039842:Neural Cell Adhesion Molecule L1 / Q000235:genetics / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D011379:Prognosis; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D013223:Statistics as Topic; D046888:Tissue Array Analysis
D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; C116884:LGR5 protein, human; D039842:Neural Cell Adhesion Molecule L1; C000606023:PROM1 protein, human; D010455:Peptides; D034741:RNA, Small Interfering; D043562:Receptors, G-Protein-Coupled