RT Journal Article
T1 Impact of Wnt/β-Catenin Inhibition on Cell Proliferation through CDC25A Downregulation in Soft Tissue Sarcomas
A1 Martinez-Font, Esther
A1 Perez-Capo, Marina
A1 Ramos, Rafael
A1 Felipe, Irene
A1 Garcias, Carmen
A1 Luna, Pablo
A1 Terrasa, Josefa
A1 Martin-Broto, Javier
A1 Vögler, Oliver
A1 Alemany, Regina
A1 Obrador-Hevia, Antonia
K1 Soft tissue sarcoma
K1 Wnt signaling
K1 β-catenin
K1 CDC25A
K1 PRI-724
K1 Trabectedin
K1 Sarcoma
K1 Vía de señalización Wnt
K1 Beta Catenina
K1 Trabectedina
AB The Wnt signaling pathway is an important cellular mechanism for regulating differentiation processes as well as cell cycle events, and different inhibitors of this pathway, for example, PRI-724, are showing promising results in clinical trials for treatment of advanced pancreatic adenocarcinoma or ovarian cancer. Growing evidence suggests that Wnt signaling may also be crucial for tumorigenesis and progression of soft tissue sarcomas (STS), a malignant neoplasm with few therapeutic options at an advanced state. Our study with several STS cell lines and primary cultures shows that inhibition of Wnt/β-catenin signaling with PRI-724 is able to suppress cell viability/proliferation and to increase cell death rates. TCF/β-catenin-mediated transcriptional activity is decreased in treated cells, leading to downregulation of its target genes CCND1 and CDC25A. The latter was critical because its downregulation via siRNA was able to mimic the effect of PRI-724 on cell cycle arrest and cell death induction. An evaluation of NCBI/GenBank data confirmed that CDC25A mRNA is elevated in STS patients. Importantly, PRI-724 in combination with standard STS chemotherapeutics doxorubicin or trabectedin enhanced their antitumoral effect in a synergistic manner according to isobolographic analysis, suggesting that Wnt inhibition through PRI-724 could be a beneficial combination regime in patients with advanced STS.
PB MDPI
YR 2020
FD 2020-09-08
LK http://hdl.handle.net/10668/4279
UL http://hdl.handle.net/10668/4279
LA en
NO Martinez-Font E, Pérez-Capó M, Ramos R, Felipe I, Garcías C, Luna P, et al. Impact of Wnt/β-Catenin Inhibition on Cell Proliferation through CDC25A Downregulation in Soft Tissue Sarcomas. Cancers. 2020 Sep 8;12(9):2556
DS RISalud
RD Apr 11, 2025