ArticleNucleic acids research2023
Identification of mechanism of cancer-cell-specific reactivation of hTERT offers therapeutic opportunities for blocking telomerase specifically in human colorectal cancer.
Article in Nucleic acids research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 32 citations in OpenAlex.
- How telomere attrition protects against cancer.Nature reviews. Genetics · 2026Review
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- Multiomics and multi-region spatial transcriptome analysis reveal cellular networks and pathways associated with HCC recurrence.JHEP reports : innovation in hepatology · 2026Article
- Telomeric Ends and Telomerase-Canonical and Non-Canonical Roles in Breast Cancer Tumorigenesis and Therapy Resistance.Biomedicines · 2026Review
- Molecular subtyping and prognostic modeling of colon adenocarcinoma based on programmed cell death features: a multi-omics and machine learning study.Frontiers in immunology · 2026Article
- Telomere Maintenance and Oncogenesis.International journal of molecular sciences · 2025Review
- Evolutionarily conserved role of telomerase reverse transcriptase in programming the microenvironment via regulation of the cGAS-STING pathway.Nature cell biology · 2025Article
- Telomeres, telomerase, and cancer: mechanisms, biomarkers, and therapeutics.Experimental hematology & oncology · 2025Review
- Norrin in cancer: from a promising prognostic biomarker to a novel therapeutic target.Frontiers in oncology · 2025Review
- PhenoMultiOmics: an enzymatic reaction inferred multi-omics network visualization web server.Bioinformatics (Oxford, England) · 2024Article
- Iron-(Fe3+)-Dependent Reactivation of Telomerase Drives Colorectal Cancers.Cancer discovery · 2024Article
- SETDB1 regulates short interspersed nuclear elements and chromatin loop organization in mouse neural precursor cells.Genome biology · 2024Article
- Recent Trends and Potential of Radiotherapy in the Treatment of Anaplastic Thyroid Cancer.Biomedicines · 2024Review
- Telomeres and telomerase in Sarcoma disease and therapy.International journal of medical sciences · 2024Review
- Regulation of telomerase towards tumor therapy.Cell & bioscience · 2023Review
- The Role of Natural Flavonoids as Telomerase Inhibitors in Suppressing Cancer Growth.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Transcriptional analysis links B cells and TERT expression to favorable prognosis in head and neck cancer.PNAS nexus · 2023Article
- Telomeres expand sphere of influence: emerging molecular impact of telomeres in non-telomeric functions.Trends in genetics : TIG · 2023Review
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transcriptional reactivation of hTERT is the limiting step in tumorigenesis. While mutations in hTERT promoter present in 19% of cancers are recognized as key drivers of hTERT reactivation, mechanisms by which wildtype hTERT (WT-hTERT) promoter is reactivated, in majority of human cancers, remain unknown. Using primary colorectal cancers (CRC) we identified Tert INTeracting region 2 (T-INT2), the critical chromatin region essential for reactivating WT-hTERT promoter in CRCs. Elevated β-catenin and JunD level in CRC facilitates chromatin interaction between hTERT promoter and T-INT2 that is necessary to turn on hTERTexpression. Pharmacological screens uncovered salinomycin, which inhibits JunD mediated hTERT-T-INT2 interaction that is required for the formation of a stable transcription complex on the hTERT promoter. Our results showed for the first time how known CRC alterations, such as APC, lead to WT-hTERT promoter reactivation during stepwise-tumorigenesis and provide a new perspective for developing cancer-specific drugs.
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