ArticleOncotarget2015
Inhibition of the Tcf/beta-catenin complex increases apoptosis and impairs adrenocortical tumor cell proliferation and adrenal steroidogenesis.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 71 citations in OpenAlex.
- OCT4 and NANOG are involved in adrenocortical tumorigenesis.Archives of endocrinology and metabolism · 2026Article
- Cyclooxygenase-2 as a potential therapeutic target in the treatment of chemoresistant glioblastomas.Medical oncology (Northwood, London, England) · 2025Review
- Adrenocortical stem cells in health and disease.Nature reviews. Endocrinology · 2025Review
- Spanish consensus on the diagnosis and management of adrenocortical carcinoma.Endocrine-related cancer · 2025Review
- PNU-74654 Induces Cell Cycle Arrest and Inhibits EMT Progression in Pancreatic Cancer.Medicina (Kaunas, Lithuania) · 2023Article
- Targeting Oncogenic Wnt/β-Catenin Signaling in Adrenocortical Carcinoma Disrupts ECM Expression and Impairs Tumor Growth.Cancers · 2023Article
- Characterising the Effect of Wnt/β-Catenin Signalling on Melanocyte Development and Patterning: Insights from Zebrafish (International journal of molecular sciences · 2023Article
- Wnt Signaling Inhibitors and Their Promising Role in Tumor Treatment.International journal of molecular sciences · 2023Review
- A reappraisal of transcriptional regulation by NR5A1 and beta-catenin in adrenocortical carcinoma.Frontiers in endocrinology · 2023Article
- Wnt/β-catenin signaling pathway in the tumor progression of adrenocortical carcinoma.Frontiers in endocrinology · 2023Review
- Heterozygous LRP1 deficiency causes developmental dysplasia of the hip by impairing triradiate chondrocytes differentiation due to inhibition of autophagy.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Wnt/β-Catenin Protects Lymphocytes from HIV-Mediated Apoptosis via Induction of Bcl-xL.Viruses · 2022Article
- What we have learnt fromHeliyon · 2022Review
- The Therapeutic Role of PNU-74654 in Hepatocellular Carcinoma May Involve Suppression of NF-κB Signaling.Medicina (Kaunas, Lithuania) · 2022Article
- PNU-74654 Suppresses TNFR1/IKB Alpha/p65 Signaling and Induces Cell Death in Testicular Cancer.Current issues in molecular biology · 2022Article
- Pediatric adrenocortical carcinoma.Frontiers in endocrinology · 2022Review
- Wnt/β-catenin signaling pathway in uterine leiomyoma: role in tumor biology and targeting opportunities.Molecular and cellular biochemistry · 2021Review
- Adrenal cortex renewal in health and disease.Nature reviews. Endocrinology · 2021Review
- Inhibition of Aurora kinase A activity enhances the antitumor response of beta-catenin blockade in human adrenocortical cancer cells.Molecular and cellular endocrinology · 2021Article
- Review
Corrections and comments
- Erratum issued
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTo date, there is no effective therapy for patients with advanced/metastatic adrenocortical cancer (ACC). The activation of the Wnt/beta-catenin signaling is frequent in ACC and this pathway is a promising therapeutic target.
aimTo investigate the effects of the inhibition of the Wnt/beta-catenin in ACC cells.
methodsAdrenal (NCI-H295 and Y1) and non-adrenal (HeLa) cell lines were treated with PNU-74654 (5-200 μM) for 24-96 h to assess cell viability (MTS-based assay), apoptosis (Annexin V), expression/localization of beta-catenin (qPCR, immunofluorescence, immunocytochemistry and western blot), expression of beta-catenin target genes (qPCR and western blot), and adrenal steroidogenesis (radioimmunoassay, qPCR and western blot).
resultsIn NCI-H295 cells, PNU-74654 significantly decreased cell proliferation 96 h after treatment, increased early and late apoptosis, decreased nuclear beta-catenin accumulation, impaired CTNNB1/beta-catenin expression and increased beta-catenin target genes 48 h after treatment. No effects were observed on HeLa cells. In NCI-H295 cells, PNU-74654 decreased cortisol, testosterone and androstenedione secretion 24 and 48 h after treatment. Additionally, in NCI-H295 cells, PNU-74654 decreased SF1 and CYP21A2 mRNA expression as well as the protein levels of STAR and aldosterone synthase 48 h after treatment. In Y1 cells, PNU-74654 impaired corticosterone secretion 24 h after treatment but did not decrease cell viability.
conclusionsBlocking the Tcf/beta-catenin complex inhibits the Wnt/beta-catenin signaling in adrenocortical tumor cells triggering increased apoptosis, decreased cell viability and impairment of adrenal steroidogenesis. These promising findings pave the way for further experiments inhibiting the Wnt/beta-catenin pathway in pre-clinical models of ACC. The inhibition of this pathway may become a promising adjuvant therapy for patients with ACC.
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