ArticleCancer research2013
Regulation of FANCD2 by the mTOR pathway contributes to the resistance of cancer cells to DNA double-strand breaks.
Article in Cancer research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 89 citations in OpenAlex.
- Amino-acids-mTORC1-driven DDA1 phosphorylation promotes DNA repair and glioblastoma progression.Cell communication and signaling : CCS · 2026Article
- Fanconi Anemia: Interplay Between DNA Repair Defects, Mitochondrial Dysfunction, and Oxidative Stress.Cells · 2026Review
- Hexavalent chromium promotes malignant transformation via enhanced translation of SUV39H1.Chemico-biological interactions · 2026Article
- Targeting the crosstalk of metabolism reprogramming and replication stress: novel strategy to combat cancer.Medical oncology (Northwood, London, England) · 2025Review
- The Role of PI3K/AKT/mTOR Signaling in Tumor Radioresistance and Advances in Inhibitor Research.International journal of molecular sciences · 2025Review
- Intrinsic differences in mTOR activity mediates lineage-specific responses to cyclophosphamide in mouse and human granulosa cells.Journal of ovarian research · 2025Article
- Protocatechuic aldehyde sensitizes BRAF-mutant melanoma cells to temozolomide through inducing FANCD2 degradation.Medical oncology (Northwood, London, England) · 2025Article
- Genome instability footprint under rapamycin and hydroxyurea treatments.PLoS genetics · 2023Article
- Radiotherapy and radio-sensitization in H3CNS neuroscience & therapeutics · 2023Review
- ATM depletion induces proteasomal degradation of FANCD2 and sensitizes neuroblastoma cells to PARP inhibitors.BMC cancer · 2023Article
- Translational Implications for Radiosensitizing Strategies in Rhabdomyosarcoma.International journal of molecular sciences · 2022Review
- Article
- Pharmacologic Induction of BRCAness inCancers · 2022Review
- Screening and identification of novel candidate biomarkers of focal cortical dysplasia type II via bioinformatics analysis.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2022Article
- FGF7-FGFR2 autocrine signaling increases growth and chemoresistance of fusion-positive rhabdomyosarcomas.Molecular oncology · 2022Article
- Deregulation of AKT-mTOR Signaling Contributes to Chemoradiation Resistance in Lung Squamous Cell Carcinoma.Molecular cancer research : MCR · 2022Article
- PI3K/Akt/mTOR Pathway and Its Role in Cancer Therapeutics: Are We Making Headway?Frontiers in oncology · 2022Review
- OGG1 in the Kidney: Beyond Base Excision Repair.Oxidative medicine and cellular longevity · 2022Review
- A Multidrug Approach to Modulate the Mitochondrial Metabolism Impairment and Relative Oxidative Stress in Fanconi Anemia Complementation Group A.Metabolites · 2021Article
- Narrative review of emerging roles for AKT-mTOR signaling in cancer radioimmunotherapy.Annals of translational medicine · 2021Review
2 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Deregulation of the mTOR pathway is closely associated with tumorigenesis. Accordingly, mTOR inhibitors such as rapamycin and mTOR-selective kinase inhibitors have been tested as cancer therapeutic agents. Inhibition of mTOR results in sensitization to DNA-damaging agents; however, the molecular mechanism is not well understood. We found that an mTOR-selective kinase inhibitor, AZD8055, significantly enhanced sensitivity of a pediatric rhabdomyosarcoma xenograft to radiotherapy and sensitized rhabdomyosarcoma cells to the DNA interstrand cross-linker (ICL) melphalan. Sensitization correlated with drug-induced downregulation of a key component of the Fanconi anemia pathway, FANCD2 through mTOR regulation of FANCD2 gene transcripts via mTORC1-S6K1. Importantly, we show that FANCD2 is required for the proper activation of ATM-Chk2 checkpoint in response to ICL and that mTOR signaling promotes ICL-induced ATM-Chk2 checkpoint activation by sustaining FANCD2. In FANCD2-deficient lymphoblasts, FANCD2 is essential to suppress endogenous and induced DNA damage, and FANCD2-deficient cells showed impaired ATM-Chk2 and ATR-Chk1 activation, which was rescued by reintroduction of wild-type FANCD2. Pharmacologic inhibition of PI3K-mTOR-AKT pathway in Rh30 rhabdomyosarcoma cells attenuated ICL-induced activation of ATM, accompanied with the decrease of FANCD2. These data suggest that the mTOR pathway may promote the repair of DNA double-strand breaks by sustaining FANCD2 and provide a novel mechanism of how the Fanconi anemia pathway modulates DNA damage response and repair.
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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.