title: Blocking of the interaction between Wnt proteins and their co-receptors contributes to the anti-tumor effects of adenovirus-mediated DKK3 in glioblastoma.
abstract: The effect of the third member of the Dickkopf family (DKK3) in the Wnt pathway in glioblastoma remains unclear. We first demonstrated the non-specific interaction of Wnt3a and Wnt5a with the receptors LRP6 and ROR2 and the up-regulation of the Wnt pathway in glioblastoma cells. We used an adenovirus vector and found that an increase in DKK3 protein attenuated the expression of Wnt3a, Wnt5a and LRP6, but not of ROR2, and their interaction, thereby affecting both canonical- and non-canonical Wnt downstream cascades. This produced anti-tumor effects in GBM xenograft models. The suppression of Wnt pathways upstream by DKK3 may have promise for the treatment of glioblastoma.
authors.affiliation: Department of Neurosurgery, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan. Electronic address: khjhkh417@yahoo.co.jp.
authors.forename: Keijiro
authors.initials: K
authors.lastname: Hara
authors.affiliation: Department of Neurosurgery, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Teruyoshi
authors.initials: T
authors.lastname: Kageji
authors.affiliation: Department of Neurosurgery, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Mizobuchi
authors.affiliation: Department of Neurosurgery, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Keiko T
authors.initials: KT
authors.lastname: Kitazato
authors.affiliation: Department of Neurosurgery, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Okazaki
authors.affiliation: Department of Neurosurgery, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Fujihara
authors.affiliation: Department of Neurosurgery, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Nakajima
authors.affiliation: Department of Neurosurgery, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Mure
authors.affiliation: Department of Neurosurgery, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Kuwayama
authors.affiliation: Faculty of Medicine, The University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Tomoyo
authors.initials: T
authors.lastname: Hara
authors.affiliation: Department of Neurosurgery, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Nagahiro
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D049109:Cell Proliferation; D018925:Chemokines; D005434:Flow Cytometry; D005822:Genetic Vectors / Q000008:administration & dosage; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D006801:Humans; D007124:Immunoenzyme Techniques; D047468:Immunoprecipitation; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D060488:Low Density Lipoprotein Receptor-Related Protein-6 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D057050:Receptor Tyrosine Kinase-like Orphan Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D051153:Wnt Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000071818:Wnt-5a Protein; D060509:Wnt3A Protein / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018925:Chemokines; C498624:DKK3 protein, human; D036341:Intercellular Signaling Peptides and Proteins; C555475:LRP6 protein, human; D060488:Low Density Lipoprotein Receptor-Related Protein-6; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; C555510:WNT3A protein, human; C085389:WNT5A protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D060509:Wnt3A Protein; C078717:ROR2 protein, human; D057050:Receptor Tyrosine Kinase-like Orphan Receptors
keywords: DKK3; Glioblastoma; LRP6; Wnt3a; Wnt5a