ArticleOncogene2016
FOXO1 is a TXN- and p300-dependent sensor and effector of oxidative stress in diffuse large B-cell lymphomas characterized by increased oxidative metabolism.
Article in Oncogene, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 45 citations in OpenAlex.
- Identification and experimental validation of CD74, PGLYRP1, and TXN as potential biomarkers in rheumatoid arthritis: an integrative bulk and ScRNA-seq study.Frontiers in immunology · 2026Article
- Molecular Mechanisms of Type 2 Diabetes-Related Heart Disease and Therapeutic Insights.International journal of molecular sciences · 2025Review
- The role of acetylation and deacetylation in cancer metabolism.Clinical and translational medicine · 2025Review
- Pannexin-3 stabilizes the transcription factor Bcl6 in a channel-independent manner to protect against vascular oxidative stress.Science signaling · 2024Article
- SIRT1 and HSP90α feed-forward circuit safeguards chromosome segregation integrity in diffuse large B cell lymphomas.Cell death & disease · 2023Article
- A Mutation in Endogenous saRNA miR-23a Influences Granulosa Cells Response to Oxidative Stress.Antioxidants (Basel, Switzerland) · 2022Article
- Expression and Prognostic Value of Glucose Transporter 3 in Diffuse Large B Cell Lymphoma.OncoTargets and therapy · 2022Article
- Redox regulation of the insulin signalling pathway.Redox biology · 2021Review
- SYK inhibition targets acute myeloid leukemia stem cells by blocking their oxidative metabolism.Cell death & disease · 2020Article
- BRAF inhibition curtails IFN-gamma-inducible PD-L1 expression and upregulates the immunoregulatory protein galectin-1 in melanoma cells.Molecular oncology · 2020Article
- CRISPR/Cas9-Mediated Foxp1 Silencing Restores Immune Surveillance in an Immunocompetent A20 Lymphoma Model.Frontiers in oncology · 2020Article
- cROSsing the Line: Between Beneficial and Harmful Effects of Reactive Oxygen Species in B-Cell Malignancies.Frontiers in immunology · 2020Review
- Mitochondrial Bioenergetics at the Onset of Drug Resistance in Hematological Malignancies: An Overview.Frontiers in oncology · 2020Review
- Targeting the thioredoxin system as a novel strategy against B-cell acute lymphoblastic leukemia.Molecular oncology · 2019Article
- Nuclear factor erythroid 2-related factors 1 and 2 are able to define the worst prognosis group among high-risk diffuse large B cell lymphomas treated with R-CHOEP.Journal of clinical pathology · 2019Article
- Heart Failure in Type 2 Diabetes Mellitus.Circulation research · 2019Review
- Gene expression profiling reveals a close relationship between follicular lymphoma grade 3A and 3B, but distinct profiles of follicular lymphoma grade 1 and 2.Haematologica · 2018Article
- New insights into redox homeostasis as a therapeutic target in B-cell malignancies.Current opinion in hematology · 2017Review
- Estradiol Suppresses TLR4-triggered Apoptosis of Decidual Stromal Cells and Drives an Anti-inflammatory TInternational journal of biological sciences · 2017Article
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Molecular profiling has led to identification of subtypes of diffuse large B-cell lymphomas (DLBCLs) differing in terms of oncogenic signaling and metabolic programs. The OxPhos-DLBCL subtype is characterized by enhanced mitochondrial oxidative phosphorylation. As increased oxidative metabolism leads to overproduction of potentially toxic reactive oxygen species (ROS), we sought to identify mechanisms responsible for adaptation of OxPhos cells to these conditions. Herein, we describe a mechanism involving the FOXO1-TXN-p300 redox-dependent circuit protecting OxPhos-DLBCL cells from ROS toxicity. We identify a BCL6-dependent transcriptional mechanism leading to relative TXN overexpression in OxPhos cells. We found that OxPhos cells lacking TXN were uniformly more sensitive to ROS and doxorubicin than control cells. Consistent with this, the overall survival of patients with high TXN mRNA expression, treated with doxorubicin-containing regimens, is significantly shorter than of those with low TXN mRNA expression. TXN overexpression curtails p300-mediated FOXO1 acetylation and its nuclear translocation in response to oxidative stress, thus attenuating FOXO1 transcriptional activity toward genes involved in apoptosis and cell cycle inhibition. We also demonstrate that FOXO1 knockdown in cells with silenced TXN expression markedly reduces ROS-induced apoptosis, indicating that FOXO1 is the major sensor and effector of oxidative stress in OxPhos-DLBCLs. These data highlight dynamic, context-dependent modulation of FOXO1 tumor-suppressor functions via acetylation and reveal potentially targetable vulnerabilities in these DLBCLs.
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