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Disruption of TCF/ß-Catenin Binding Impairs Wnt Signaling and Induces Apoptosis in Soft Tissue Sarcoma Cells.
Martinez-Font, Esther; Felipe-Abrio, Irene; Calabuig-Fariñas, Silvia; Ramos, Rafael; Terrasa, Josefa; Vögler, Oliver; Alemany, Regina; Martín-Broto, Javier; Obrador-Hevia, Antònia.
Affiliation
  • Martinez-Font E; Group of Advanced Therapies and Biomarkers in Clinical Oncology, Institut d'Investigació Sanitària de Palma (IdISPa), Palma de Mallorca, Spain.
  • Felipe-Abrio I; Group of Molecular Oncology and New Therapies, Oncohematology and Genetics Department, Instituto de Biomedicina de Sevilla (IBiS), Sevilla, Spain.
  • Calabuig-Fariñas S; Molecular Oncology Laboratory, Fundación de Investigación, Hospital General Universitario de Valencia, Valencia, Spain.
  • Ramos R; Department of Pathology, Universitat de Valencia, Valencia, Spain.
  • Terrasa J; Department of Pathology, Hospital Universitari Son Espases, Palma de Mallorca, Spain.
  • Vögler O; Group of Advanced Therapies and Biomarkers in Clinical Oncology, Institut d'Investigació Sanitària de Palma (IdISPa), Palma de Mallorca, Spain.
  • Alemany R; Department of Oncology, Hospital Universitari Son Espases, Palma de Mallorca, Spain.
  • Martín-Broto J; Group of Advanced Therapies and Biomarkers in Clinical Oncology, Institut d'Investigació Sanitària de Palma (IdISPa), Palma de Mallorca, Spain.
  • Obrador-Hevia A; Group of Clinical and Translational Research, Department of Biology, Institut Universitari d'Investigacions en Ciències de la Salut (IUNICS), University of the Balearic Islands, Spain.
Mol Cancer Ther ; 16(6): 1166-1176, 2017 06.
Article in En | MEDLINE | ID: mdl-28292937
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/ß-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/ß-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 ß-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.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Sarcoma / Apoptosis / Beta Catenin / TCF Transcription Factors / Wnt Signaling Pathway Limits: Humans Language: En Journal: Mol Cancer Ther Journal subject: ANTINEOPLASICOS Year: 2017 Document type: Article Affiliation country: Country of publication:

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Sarcoma / Apoptosis / Beta Catenin / TCF Transcription Factors / Wnt Signaling Pathway Limits: Humans Language: En Journal: Mol Cancer Ther Journal subject: ANTINEOPLASICOS Year: 2017 Document type: Article Affiliation country: Country of publication: