Martinez-Font, EstherPerez-Capo, MarinaRamos, RafaelFelipe, IreneGarcias, CarmenLuna, PabloTerrasa, JosefaMartin-Broto, JavierVögler, OliverAlemany, ReginaObrador-Hevia, Antonia2022-10-252022-10-252020-09-08Martinez-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):2556http://hdl.handle.net/10668/4279The 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.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/Soft tissue sarcomaWnt signalingβ-cateninCDC25APRI-724TrabectedinSarcomaVía de señalización WntBeta CateninaTrabectedinaMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Phenomena and Processes::Chemical Phenomena::Chemical Processes::Biochemical Processes::Signal Transduction::Wnt Signaling PathwayMedical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Antisense Elements (Genetics)::RNA, Antisense::RNA, Small InterferingMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell SurvivalMedical Subject Headings::Diseases::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Glandular and Epithelial::Carcinoma::AdenocarcinomaMedical Subject Headings::Information Science::Information Science::Information Storage and Retrieval::Databases as Topic::Databases, Factual::Databases, Genetic::Databases, Nucleic AcidMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation::Down-RegulationMedical Subject Headings::Diseases::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Pancreatic NeoplasmsMedical Subject Headings::Phenomena and Processes::Physiological Phenomena::Physiological Processes::Growth and Development::Growth::Cell Growth Processes::Cell ProliferationMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell CycleMedical Subject Headings::Chemicals and Drugs::Carbohydrates::Glycosides::Aminoglycosides::Anthracyclines::Daunorubicin::DoxorubicinMedical Subject Headings::Diseases::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Connective and Soft TissueMedical Subject Headings::Diseases::Neoplasms::Neoplasms by Site::Endocrine Gland Neoplasms::Ovarian NeoplasmsMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Cycle::Cell Cycle CheckpointsMedical Subject Headings::Diseases::Neoplasms::Neoplastic Processes::CarcinogenesisMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell DeathMedical Subject Headings::Anatomy::Cells::Cells, Cultured::Cell LineMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Cytoskeletal Proteins::CateninsMedical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA::RNA, Messengerresearch article32911761open accessRegulación hacia abajoVía de señalización WntMuerte celularTerapéuticaCateninasCiclo celularARN mensajeroDoxorrubicinaBases de datos de ácidos nucleicosNeoplasiasSarcoma10.3390/cancers120925562072-6694PMC7564873