ArticleOncotarget2015
DNA damage-induced S and G2/M cell cycle arrest requires mTORC2-dependent regulation of Chk1.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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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.
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Who cites it
39 citing papers in PubMed, 68 citations in OpenAlex.
- GSK3i combinatorial treatments affect CDK4/6 and compensatory pathways in 3D preclinical models of pancreatic neuroendocrine tumors.Biology open · 2026Article
- Induction of Triple-Negative Breast Cancer Cell Death and Chemosensitivity Using mTORC2-Directed RNAi Nanomedicine.Cancer research communications · 2025Article
- Rescuing DNMT1 fails to fully reverse the molecular and functional repercussions of its loss in mouse embryonic stem cells.Nucleic acids research · 2025Article
- Therapeutic effect of three-dimensional hanging drop cultured human umbilical cord mesenchymal stem cells on osteoarthritis in rabbits.Stem cell research & therapy · 2024Article
- XPO1 Enables Adaptive Regulation of mRNA Export Required for Genotoxic Stress Tolerance in Cancer Cells.Cancer research · 2024Article
- GSE1 links the HDAC1/CoREST co-repressor complex to DNA damage.Nucleic acids research · 2023Article
- Article
- Targeting mTOR for Anti-Aging and Anti-Cancer Therapy.Molecules (Basel, Switzerland) · 2023Review
- Nutri-stress, mitochondrial dysfunction, and insulin resistance-role of heat shock proteins.Cell stress & chaperones · 2023Review
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- Anti-HIV Drugs Cause Mitochondrial Dysfunction in Monocyte-Derived Macrophages.Antimicrobial agents and chemotherapy · 2022Article
- Flavonoids-Natural Gifts to Promote Health and Longevity.International journal of molecular sciences · 2022Review
- Narrative review of emerging roles for AKT-mTOR signaling in cancer radioimmunotherapy.Annals of translational medicine · 2021Review
- Regulation of DNA duplication by the mTOR signaling pathway.Cell cycle (Georgetown, Tex.) · 2021Review
- mTORC1 Crosstalk With Stress Granules in Aging and Age-Related Diseases.Frontiers in aging · 2021Review
- Targeting the PI3K/mTOR Pathway Augments CHK1 Inhibitor-Induced Replication Stress and Antitumor Activity in High-Grade Serous Ovarian Cancer.Cancer research · 2020Article
- Aflatoxin B1 Induces Neurotoxicity through Reactive Oxygen Species Generation, DNA Damage, Apoptosis, and S-Phase Cell Cycle Arrest.International journal of molecular sciences · 2020Article
- A Fluorinated Phenylbenzothiazole Arrests the Trypanosoma cruzi Cell Cycle and Diminishes the Infection of Mammalian Host Cells.Antimicrobial agents and chemotherapy · 2020Article
- An mTORC1/2 dual inhibitor, AZD2014, acts as a lysosomal function activator and enhances gemtuzumab ozogamicin-induced apoptosis in primary human leukemia cells.International journal of hematology · 2019Article
- Biological Characteristics of Cervical Precancerous Cell Proliferation.Open medicine (Warsaw, Poland) · 2019Article
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4 authors at 2 institutions in 2 countries.
Funding
Abstract
mTOR signalling is commonly dysregulated in cancer. Concordantly, mTOR inhibitors have demonstrated efficacy in a subset of tumors and are in clinical trials as combination therapies. Although mTOR is associated with promoting cell survival after DNA damage, the exact mechanisms are not well understood. Moreover, since mTOR exists as two complexes, mTORC1 and mTORC2, the role of mTORC2 in cancer and in the DNA damage response is less well explored. Here, we report that mTOR protein levels and kinase activity are transiently increased by DNA damage in an ATM and ATR-dependent manner. We show that inactivation of mTOR with siRNA or pharmacological inhibition of mTORC1/2 kinase prevents etoposide-induced S and G2/M cell cycle arrest. Further results show that Chk1, a key regulator of the cell cycle arrest, is important for this since ablation of mTOR prevents DNA damage-induced Chk1 phosphorylation and decreases Chk1 protein production. Furthermore, mTORC2 was essential and mTORC1 dispensable, for this role. Importantly, we show that mTORC1/2 inhibition sensitizes breast cancer cells to chemotherapy. Taken together, these results suggest that breast cancer cells may rely on mTORC2-Chk1 pathway for survival and provide evidence that mTOR kinase inhibitors may overcome resistance to DNA-damage based therapies in breast cancer.
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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.