ArticleScientific reports2017
Regulation of CHK1 by mTOR contributes to the evasion of DNA damage barrier of cancer cells.
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 25 papers.
What it found
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Who cites it
25 citing papers in PubMed, 47 citations in OpenAlex.
- The STK33/mTORC1/S6K1/HIF-1α signalling axis drives glycolysis and progression in pancreatic neuroendocrine tumours.Journal of translational medicine · 2026Article
- Surface-engineered dual drug-loaded tumor-targeted liposomal nanoparticles to overcome the therapeutic resistance in glioblastoma multiforme.Communications medicine · 2026Article
- Targeting the crosstalk of metabolism reprogramming and replication stress: novel strategy to combat cancer.Medical oncology (Northwood, London, England) · 2025Review
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- Sensitization of FOLFOX-resistant colorectal cancer cells via the modulation of a novel pathway involving protein phosphatase 2A.iScience · 2022Article
- CRLF2 overexpression results in reduced B-cell differentiation and upregulated E2F signaling in the Dp16 mouse model of Down syndrome.Experimental hematology · 2022Article
- Deregulation of AKT-mTOR Signaling Contributes to Chemoradiation Resistance in Lung Squamous Cell Carcinoma.Molecular cancer research : MCR · 2022Article
- Narrative review of emerging roles for AKT-mTOR signaling in cancer radioimmunotherapy.Annals of translational medicine · 2021Review
- Proteins from the DNA Damage Response: Regulation, Dysfunction, and Anticancer Strategies.Cancers · 2021Review
- Targeted radioimmunotherapy with the iodine-131-labeled caerin 1.1 peptide for human anaplastic thyroid cancer in nude mice.Annals of nuclear medicine · 2021Article
- Regulation of DNA duplication by the mTOR signaling pathway.Cell cycle (Georgetown, Tex.) · 2021Review
- Phosphoinositide 3-Kinase (PI3K) Reactive Oxygen Species (ROS)-Activated Prodrug in Combination with Anthracycline Impairs PI3K Signaling, Increases DNA Damage Response and Reduces Breast Cancer Cell Growth.International journal of molecular sciences · 2021Article
- Phosphorylation regulates cullin-based ubiquitination in tumorigenesis.Acta pharmaceutica Sinica. B · 2021Review
- Inhibition of Nuclear Pore Complex Formation Selectively Induces Cancer Cell Death.Cancer discovery · 2021Article
- Regulation of the error-prone DNA polymerase Polκ by oncogenic signaling and its contribution to drug resistance.Science signaling · 2020Article
- Inhibition of CHK 1 (Checkpoint Kinase 1) Elicits Therapeutic Effects in Pulmonary Arterial Hypertension.Arteriosclerosis, thrombosis, and vascular biology · 2019Article
- Inhibiting BRAF Oncogene-Mediated Radioresistance Effectively Radiosensitizes BRAFClinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
- Article
- mTOR Signaling Upregulates CDC6 via Suppressing miR-3178 and Promotes the Loading of DNA Replication Helicase.Scientific reports · 2019Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
Oncogenic transformation leads to dysregulated cell proliferation, nutrient deficiency, and hypoxia resulting in metabolic stress and increased DNA damage. In normal cells, such metabolic stress leads to inhibition of signaling through the mammalian Target of Rapamycin Complex 1 (mTORC1), reduction of protein translation, cell cycle arrest, and conservation of energy. In contrast, negative regulation of mTORC1 signaling by DNA damage is abrogated in many cancer cells, thus mTORC1 signaling remains active under microenvironmental conditions that potentially promote endogenous DNA damage. Here we report that mTORC1 signaling suppresses endogenous DNA damage and replication stress. Pharmacological inhibition of mTOR signaling resulted in phosphorylation of H2AX concomitant with the decrease of CHK1 levels both in cell culture and mouse rhadomyosarcoma xenografts. Further results demonstrated that mTORC1-S6K1 signaling controls transcription of CHK1 via Rb-E2F by upregulating cyclin D and E. Consistent with these results, downregulation of CHK1 by inhibition of mTOR kinase resulted in defects in the slow S phase progression following DNA damage. These results indicate that, under stressful conditions, maintained mTORC1 signaling in cancer cells promotes survival by suppressing endogenous DNA damage, and may control cell fate through the regulation of CHK1.
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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.