ArticleChemical research in toxicology2016
Kynurenine Signaling Increases DNA Polymerase Kappa Expression and Promotes Genomic Instability in Glioblastoma Cells.
Article in Chemical research in toxicology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 38 citations in OpenAlex.
- The Kynurenine Pathway: Unraveling Its Role in Neurological Disorders via Mammalian Cellular Models.International journal of molecular sciences · 2026Review
- Aryl Hydrocarbon Receptor Signaling in Aging: A Key Modulator of Brain Homeostasis.Molecular neurobiology · 2026Review
- Implications of DNA damage response and immunotherapy in tumor therapy.Cell communication and signaling : CCS · 2025Review
- Human TLS DNA polymerase: saviors or threats under replication stress?Molecular and cellular biochemistry · 2025Review
- Targeting hypoxia-mediated chemo-immuno resistance by a hybrid NBDHEX-Pt(IV) prodrug via declining nuclear STING1-promoted AhR-CIN in human lung squamous cell carcinoma.Translational oncology · 2025Article
- Review
- AT-0174, a novel dual IDO1/TDO2 enzyme inhibitor, synergises with temozolomide to improve survival in an orthotopic mouse model of glioblastoma.BMC cancer · 2024Article
- Temozolomide resistance mechanisms: unveiling the role of translesion DNA polymerase kappa in glioblastoma spheroids in vitro.Bioscience reports · 2024Article
- Implications of Translesion DNA Synthesis Polymerases on Genomic Stability and Human Health.Molecular and cellular biology · 2023Article
- The kynurenine pathway presents multi-faceted metabolic vulnerabilities in cancer.Frontiers in oncology · 2023Review
- The Kynurenine Pathway and Cancer: Why Keep It Simple When You Can Make It Complicated.Cancers · 2022Review
- Cell-based immunotherapy of glioblastoma multiforme.Oncology letters · 2022Review
- DNA damage repair in glioblastoma: current perspectives on its role in tumour progression, treatment resistance and PIKKing potential therapeutic targets.Cellular oncology (Dordrecht, Netherlands) · 2021Review
- Review
- Inhibition of tryptophan 2,3-dioxygenase impairs DNA damage tolerance and repair in glioma cells.NAR cancer · 2021Article
- Targeting translesion synthesis (TLS) to expose replication gaps, a unique cancer vulnerability.Expert opinion on therapeutic targets · 2021Review
- DNA Damage Tolerance Pathways in Human Cells: A Potential Therapeutic Target.Frontiers in oncology · 2021Review
- A Comprehensive Pan-Cancer Analysis of 33 Human Cancers Reveals the Immunotherapeutic Value of Aryl Hydrocarbon Receptor.Frontiers in immunology · 2021Article
- Immunosuppressive IDO in Cancer: Mechanisms of Action, Animal Models, and Targeting Strategies.Frontiers in immunology · 2020Review
- Glioblastoma chemoresistance: roles of the mitochondrial melatonergic pathway.Cancer drug resistance (Alhambra, Calif.) · 2020Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Overexpression of the translesion synthesis polymerase hpol κ in glioblastomas has been linked to poor patient prognosis; however, the mechanism promoting higher expression in these tumors remains unknown. We determined that activation of the aryl hydrocarbon receptor (AhR) pathway in glioblastoma cells leads to increased hpol κ mRNA and protein levels. We blocked nuclear translocation and DNA binding by AhR in glioblastoma cells using a small-molecule and observed decreased hpol κ expression. Pharmacological inhibition of tryptophan-2,3-dioxygenase (TDO), the enzyme largely responsible for activating AhR in glioblastoma, led to a decrease in the endogenous AhR agonist kynurenine and a corresponding decrease in hpol κ protein levels. Importantly, we discovered that inhibiting TDO activity, AhR signaling, or suppressing hpol κ expression with RNA interference led to decreased chromosomal damage in glioblastoma cells. Epistasis assays further supported the idea that TDO activity, activation of AhR signaling, and the resulting overexpression of hpol κ function primarily in the same pathway to increase endogenous DNA damage. These findings indicate that upregulation of hpol κ through glioblastoma-specific TDO activity and activation of AhR signaling likely contributes to the high levels of replication stress and genomic instability observed in these tumors.
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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.