Blocking of the interaction between Wnt proteins and their co-receptors contributes to the anti-tumor effects of adenovirus-mediated DKK3 in glioblastoma
K Hara, T Kageji, Y Mizobuchi, KT Kitazato, T Okazaki… - Cancer letters, 2015 - Elsevier
K Hara, T Kageji, Y Mizobuchi, KT Kitazato, T Okazaki, T Fujihara, K Nakajima, H Mure…
Cancer letters, 2015•ElsevierThe 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 …
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 …
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.
Elsevier