ArticleScientific reports2017
Activating Akt1 mutations alter DNA double strand break repair and radiosensitivity.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.
- Effect of AKT1 (p. E17K) Hotspot Mutation on Malignant Tumorigenesis and Prognosis.Frontiers in cell and developmental biology · 2020Pooled it
- Expression of HGF, pMet, and pAkt is related to benefit of radiotherapy after breast-conserving surgery: a long-term follow-up of the SweBCG91-RT randomised trial.Molecular oncology · 2020Trial
- Moesin silencing enhances the radiosensitivity of glioblastoma by inhibiting DNA damage repair via CD44/AKT1 signaling pathway.Discover oncology · 2025Article
- The Role of PI3K/AKT/mTOR Signaling in Tumor Radioresistance and Advances in Inhibitor Research.International journal of molecular sciences · 2025Review
- Genome rearrangements induced by the stimulation of end-joining of DNA double strand breaks through multiple phosphorylation of MRE11 by the kinase PKB/AKT1.Nucleic acids research · 2025Article
- DNA-PKcs/AKT1 inhibits epithelial-mesenchymal transition during radiation-induced pulmonary fibrosis by inducing ubiquitination and degradation of Twist1.Clinical and translational medicine · 2024Article
- Combined PARP inhibitors and small molecular inhibitors in solid tumor treatment (Review).International journal of oncology · 2023Review
- Targeting HER3-dependent activation of nuclear AKT improves radiotherapy of non-small cell lung cancer.Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology · 2022Article
- Development and Evolution of DNA-Dependent Protein Kinase Inhibitors toward Cancer Therapy.International journal of molecular sciences · 2022Review
- Investigation into Chronic Low-Dose Ionizing Radiation Effect on Gene Expression Profile of Human HUVECs Cells.Journal of lasers in medical sciences · 2022Article
- Targeting AKT-Dependent Regulation of Antioxidant Defense Sensitizes AKT-E17K Expressing Cancer Cells to Ionizing Radiation.Frontiers in oncology · 2022Article
- Review
- A New Twist in Protein Kinase B/Akt Signaling: Role of Altered Cancer Cell Metabolism in Akt-Mediated Therapy Resistance.International journal of molecular sciences · 2020Review
- Article
- The potential drug for treatment in pancreatic adenocarcinoma: a bioinformatical study based on distinct drug databases.Chinese medicine · 2020Article
- Review
- Regulation of tumor cell - Microenvironment interaction by the autotaxin-lysophosphatidic acid receptor axis.Advances in biological regulation · 2019Review
- Restraining Akt1 Phosphorylation Attenuates the Repair of Radiation-Induced DNA Double-Strand Breaks and Reduces the Survival of Irradiated Cancer Cells.International journal of molecular sciences · 2018Article
- Review
- Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The survival kinase Akt has clinical relevance to radioresistance. However, its contributions to the DNA damage response, DNA double strand break (DSB) repair and apoptosis remain poorly defined and often contradictory. We used a genetic approach to explore the consequences of genetic alterations of Akt1 for the cellular radiation response. While two activation-associated mutants with prominent nuclear access, the phospho-mimicking Akt1-TDSD and the clinically relevant PH-domain mutation Akt1-E17K, accelerated DSB repair and improved survival of irradiated Tramp-C1 murine prostate cancer cells and Akt1-knockout murine embryonic fibroblasts in vitro, the classical constitutively active membrane-targeted myrAkt1 mutant had the opposite effects. Interestingly, DNA-PKcs directly phosphorylated Akt1 at S473 in an in vitro kinase assay but not vice-versa. Pharmacological inhibition of DNA-PKcs or Akt restored radiosensitivity in tumour cells expressing Akt1-E17K or Akt1-TDSD. In conclusion, Akt1-mediated radioresistance depends on its activation state and nuclear localization and is accessible to pharmacologic inhibition.
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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.