%0 Journal Article
%A Martinez-Font, Esther
%A Felipe-Abrio, Irene
%A Calabuig-Fariñas, Silvia
%A Ramos, Rafael
%A Terrasa, Josefa
%A Vögler, Oliver
%A Alemany, Regina
%A Martín-Broto, Javier
%A Obrador-Hevia, Antònia
%T Disruption of TCF/β-Catenin Binding Impairs Wnt Signaling and Induces Apoptosis in Soft Tissue Sarcoma Cells.
%D 2017
%U http://hdl.handle.net/10668/10962
%X Soft tissue sarcomas (STS) are malignant tumors of mesenchymal origin and represent around 1% of adult cancers, being a very heterogeneous group of tumors with more than 50 different subtypes. The Wnt signaling pathway is involved in the development and in the regulation, self-renewal, and differentiation of mesenchymal stem cells, and plays a role in sarcomagenesis. In this study, we have tested pharmacologic inhibition of Wnt signaling mediated by disruption of TCF/β-catenin binding and AXIN stabilization, being the first strategy more efficient in reducing cell viability and downstream effects. We have shown that disruption of TCF/β-catenin binding with PKF118-310 produces in vitro antitumor activity in a panel of prevalent representative STS cell lines and primary cultures. At the molecular level, PKF118-310 treatment reduced β-catenin nuclear localization, reporter activity, and target genes, resulting in an increase in apoptosis. Importantly, combination of PKF118-310 with doxorubicin resulted in enhanced reduction of cell viability, suggesting that Wnt inhibition could be a new combination regime in these patients. Our findings support the usefulness of Wnt inhibitors as new therapeutic strategies for the prevalent STS. Mol Cancer Ther; 16(6); 1166-76. ©2017 AACR.
%K Antineoplastic Agents
%K Cell Cycle
%K Doxorubicin
%K Humans
%K Pyrimidinones
%K Sarcoma
%K Triazines
%K beta Catenin
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