ArticleThe Journal of biological chemistry2012
Human telomerase reverse transcriptase (hTERT) is a novel target of the Wnt/β-catenin pathway in human cancer.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 111 papers.
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Who cites it
111 citing papers in PubMed, 175 citations in OpenAlex.
- The Telomerase Reverse Transcriptase (TERT) Gene Molecular Characterization in Sheep and the Association of Its Variation with Wool Traits.Animals : an open access journal from MDPI · 2026Article
- Targeting ferroptosis induction via nanomaterials in hepatocellular carcinoma: an insight into mechanism and therapeutic potential.Journal of nanobiotechnology · 2026Review
- Improvement of fertility in female mice by treatment with novel telomerase-increasing compounds.Reproductive biology and endocrinology : RB&E · 2026Article
- Telomere Maintenance and Oncogenesis.International journal of molecular sciences · 2025Review
- Modified hTERT promoters-driven purine nucleoside phosphorylase-gene therapy in association with chemo- and targeted therapy in the context of ovarian cancer.Cancer gene therapy · 2025Article
- Beyond Telomeres: Unveiling the Extratelomeric Functions of TERT in B-Cell Malignancies.Cancers · 2025Review
- Geographic and Viral Etiology Patterns ofInternational journal of molecular sciences · 2025Review
- Canonical and non-canonical functions of the non-coding RNA component (TERC) of telomerase complex.Cell & bioscience · 2025Review
- Comparative Analysis of Primary Ovarian Cancer Cells and Established Cell Lines as a New Tool for Studies on Ovarian Cancer Cell Complexity.International journal of molecular sciences · 2024Article
- The evolving roles of Wnt signaling in stem cell proliferation and differentiation, the development of human diseases, and therapeutic opportunities.Genes & diseases · 2024Review
- Favipiravir, an antiviral drug, in combination with tamoxifen exerts synergistic effect in tamoxifen-resistant breast cancer cells via hTERT inhibition.Scientific reports · 2024Article
- Molecular mechanisms and therapeutic potential of lithium in Alzheimer's disease: repurposing an old class of drugs.Frontiers in pharmacology · 2024Review
- Combining old and new concepts in targeting telomerase for cancer therapy: transient, immediate, complete and combinatory attack (TICCA).Cancer cell international · 2023Review
- Advancements in clinical aspects of targeted therapy and immunotherapy in breast cancer.Molecular cancer · 2023Review
- Article
- The Relevance of Telomerase and Telomere-Associated Proteins in B-Acute Lymphoblastic Leukemia.Genes · 2023Review
- Lithium Prevents Telomere Shortening in Cortical Neurons in Amyloid-Beta Induced Toxicity.NeuroSci · 2023Article
- Identification of mechanism of cancer-cell-specific reactivation of hTERT offers therapeutic opportunities for blocking telomerase specifically in human colorectal cancer.Nucleic acids research · 2023Article
- Chicken telomerase reverse transcriptase promotes the tumorigenicity of avian leukosis virus subgroup J by regulating the Wnt/β-catenin signaling pathway.Veterinary research · 2022Article
- Article
51 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Telomerase activation plays a critical role in human carcinogenesis through the maintenance of telomeres, but the activation mechanism during carcinogenesis remains unclear. The human telomerase reverse transcriptase (hTERT) promoter has been shown to promote hTERT gene expression selectively in tumor cells but not in normal cells. Deregulation of the Wnt/β-catenin signaling pathway is reported to be associated with human carcinogenesis. However, little is known about whether the Wnt/β-catenin pathway is involved in activating hTERT transcription and inducing telomerase activity (TA). In this study, we report that hTERT is a novel target of the Wnt/β-catenin pathway. Transient activation of the Wnt/β-catenin pathway either by transfection of a constitutively active form of β-catenin or by LiCl or Wnt-3a conditioned medium treatment induced hTERT mRNA expression and elevated TA in different cell lines. Furthermore, we found that silencing endogenous β-catenin expression by β-catenin gene-specific shRNA effectively decreased hTERT expression, suppressed TA, and accelerated telomere shortening. Of the four members of the lymphoid-enhancing factor (LEF)/T-cell factor (TCF) family, only TCF4 showed more effective stimulation on the hTERT promoter. Ectopic expression of a dominant negative form of TCF4 inhibited hTERT expression in cancer cells. Through promoter mapping, electrophoretic mobility shift assay, and chromatin immunoprecipitation assay, we found that hTERT is a direct target of β-catenin·TCF4-mediated transcription and that the TCF4 binding site at the hTERT promoter is critical for β-catenin·TCF4-dependent expression regulation. Given the pivotal role of telomerase in carcinogenesis, these results may offer insight into the regulation of telomerase in human cancer.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.