2024-03-29T04:39:56Zhttp://repisalud.isciii.es/oai/requestoai:repisalud.isciii.es:20.500.12105/110742023-10-06T08:16:32Zcom_20.500.12105_2174com_20.500.12105_2051com_20.500.12105_2173col_20.500.12105_2175
00925njm 22002777a 4500
dc
Martinez-Font, Esther
author
Pérez-Capó, Marina
author
Ramos, Rafael
author
Garcías, Carmen
author
Luna, Pablo
author
Terrasa, Josefa
author
Martín-Broto, Javier
author
Vögler, Oliver
author
Alemany, Regina
author
Obrador-Hevia, Antònia
author
Felipe-Abrio, Irene
author
2020-09-08
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.
Cancers (Basel) . 2020 ;12(9):E2556.
2072-6694
http://hdl.handle.net/20.500.12105/11074
32911761
10.3390/cancers12092556
Cancers
Soft tissue sarcoma
Wnt signaling
β-catenin
CDC25A
PRI-724
Impact of Wnt/β-Catenin Inhibition on Cell Proliferation through CDC25A Downregulation in Soft Tissue Sarcomas.