%0 Journal Article
%T Dickkopf-1 Inhibition Reactivates Wnt/β-Catenin Signaling in Rhabdomyosarcoma, Induces Myogenic Markers In Vitro and Impairs Tumor Cell Survival In Vivo.
%A Giralt I
%A Gallo-Oller G
%A Navarro N
%A Zarzosa P
%A Pons G
%A Magdaleno A
%A Segura MF
%A Sábado C
%A Hladun R
%A Arango D
%A Sánchez de Toledo J
%A Moreno L
%A Gallego S
%A Roma J
%J Int J Mol Sci
%V 22
%N 23
%D Nov 2021 29
%M 34884726
%F 6.208
%R 10.3390/ijms222312921
%X The Wnt/β-catenin signaling pathway plays a pivotal role during embryogenesis and its deregulation is a key mechanism in the origin and progression of several tumors. Wnt antagonists have been described as key modulators of Wnt/β-catenin signaling in cancer, with Dickkopf-1 (DKK-1) being the most studied member of the DKK family. Although the therapeutic potential of DKK-1 inhibition has been evaluated in several diseases and malignancies, little is known in pediatric tumors. Only a few works have studied the genetic inhibition and function of DKK-1 in rhabdomyosarcoma. Here, for the first time, we report the analysis of the therapeutic potential of DKK-1 pharmaceutical inhibition in rhabdomyosarcoma, the most common soft tissue sarcoma in children. We performed DKK-1 inhibition via shRNA technology and via the chemical inhibitor WAY-2626211. Its inhibition led to β-catenin activation and the modulation of focal adhesion kinase (FAK), with positive effects on in vitro expression of myogenic markers and a reduction in proliferation and invasion. In addition, WAY-262611 was able to impair survival of tumor cells in vivo. Therefore, DKK-1 could constitute a molecular target, which could lead to novel therapeutic strategies in RMS, especially in those patients with high DKK-1 expression.