ArticleOncotarget2017
Kras mutations increase telomerase activity and targeting telomerase is a promising therapeutic strategy for Kras-mutant NSCLC.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
21 citing papers in PubMed, 38 citations in OpenAlex.
- Functional Precision in Pancreatic Cancer: Redefining Biomarkers with Patient-Derived Organoids.International journal of molecular sciences · 2025Review
- Mechanisms and current advances in treatingChinese medical journal pulmonary and critical care medicine · 2025Review
- A New Dawn for Targeted Cancer Therapy: Small Molecule Covalent Binding Inhibitor Targeting K-Ras (G12C).Current medicinal chemistry · 2025Review
- Beginning at the ends: telomere and telomere-based cancer therapeutics.Molecular genetics and genomics : MGG · 2024Review
- Targeting telomeres: advances in telomere maintenance mechanism-specific cancer therapies.Nature reviews. Cancer · 2022Review
- Tieing together loose ends: telomere instability in cancer and aging.Molecular oncology · 2022Review
- Epigenetics alternation in lung fibrosis and lung cancer.Frontiers in cell and developmental biology · 2022Review
- Review
- KRAS mutation: from undruggable to druggable in cancer.Signal transduction and targeted therapy · 2021Review
- Shelterin complex gene: Prognosis and therapeutic vulnerability in cancer.Biochemistry and biophysics reports · 2021Review
- Article
- ORN: Inferring patient-specific dysregulation status of pathway modules in cancer with OR-gate Network.PLoS computational biology · 2021Article
- [Clinical Application and Challenges of Telomere and Telomerase Research in Lung Cancer].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2021Review
- The Renaissance of KRAS Targeting in Advanced Non-Small-Cell Lung Cancer: New Opportunities Following Old Failures.Frontiers in oncology · 2021Review
- Different TERT Expression between Colorectal Adenoma and Serrated Polyp.Medicina (Kaunas, Lithuania) · 2020Article
- Implications of telomerase reverse transcriptase in tumor metastasis.BMB reports · 2020Review
- Inhibition of DDR1 enhances in vivo chemosensitivity in KRAS-mutant lung adenocarcinoma.JCI insight · 2020Article
- Telomeres and telomerase in oncogenesis.Oncology letters · 2020Review
- A Driver Never Works Alone-Interplay Networks of Mutant p53, MYC, RAS, and Other Universal Oncogenic Drivers in Human Cancer.Cancers · 2020Review
- Macrophage Origin, Metabolic Reprogramming and IL-1 Signaling: Promises and Pitfalls in Lung Cancer.Cancers · 2019Review
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Authors and funding
16 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
As shortened telomeres inhibit tumor formation and prolong life span in a KrasG12D mouse lung cancer model, we investigated the implications of telomerase in Kras-mutant NSCLC. We found that Kras mutations increased TERT (telomerase reverse transcriptase) mRNA expression and telomerase activity and telomere length in both immortalized bronchial epithelial cells (BEAS-2B) and lung adenocarcinoma cells (Calu-3). MEK inhibition led to reduced TERT expression and telomerase activity. Furthermore, telomerase inhibitor BIBR1532 shortened telomere length and inhibited mutant Kras-induced long-term proliferation, colony formation and migration capabilities of BEAS-2B and Calu-3 cells. Importantly, BIBR1532 sensitized oncogenic Kras expressing Calu-3 cells to chemotherapeutic agents. The Calu-3-KrasG12D xenograft mouse model confirmed that BIBR1532 enhanced the antitumor efficacy of paclitaxel in vivo. In addition, higher TERT expression was seen in Kras-mutant NSCLC than that with wild-type Kras. Our data suggest that Kras mutations increase telomerase activity and telomere length by activating the RAS/MEK pathway, which contributes to an aggressive phenotype of NSCLC. Kras mutations-induced lung tumorigenesis and chemoresistance are attenuated by telomerase inhibition. Targeting telomerase/telomere may be a promising therapeutic strategy for patients with Kras-mutant NSCLC.
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Registered trials
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.