ArticleOncogenesis2020
Notch3 contributes to T-cell leukemia growth via regulation of the unfolded protein response.
Article in Oncogenesis, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Brain-Targeted Delivery of Phenformin Using Phospholipid and Non-Phospholipid Vesicles for SHH Medulloblastoma.Nanomaterials (Basel, Switzerland) · 2026Article
- Prolyl-isomerase Pin1 drives platinum resistance by regulating Notch3 stability and function in ovarian cancer.Journal of experimental & clinical cancer research : CR · 2026Article
- NOTCH3 attenuates cytotoxicity via RBPJ-dependent PVR upregulation to influence immunotherapy outcomes in colorectal cancer.Frontiers in immunology · 2026Article
- Review
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- QRICH1 suppresses pediatric T-cell acute lymphoblastic leukemia by inhibiting GRP78.Cell death & disease · 2024Article
- Thymic-Epithelial-Cell-Dependent Microenvironment Influences Proliferation and Apoptosis of Leukemic Cells.International journal of molecular sciences · 2024Article
- SCF and IL-33 regulate mouse mast cell phenotypic and functional plasticity supporting a pro-inflammatory microenvironment.Cell death & disease · 2023Article
- Current Opportunities for Targeting Dysregulated Neurodevelopmental Signaling Pathways in Glioblastoma.Cells · 2022Review
- Review
- 3-Ketodihydrosphingosine reductase maintains ER homeostasis and unfolded protein response in leukemia.Leukemia · 2022Article
- 5FU/Oxaliplatin-Induced Jagged1 Cleavage Counteracts Apoptosis Induction in Colorectal Cancer: A Novel Mechanism of Intrinsic Drug Resistance.Frontiers in oncology · 2022Article
- The role and therapeutic implication of endoplasmic reticulum stress in inflammatory cancer transformation.American journal of cancer research · 2022Review
- Notch-Signaling Deregulation Induces Myeloid-Derived Suppressor Cells in T-Cell Acute Lymphoblastic Leukemia.Frontiers in immunology · 2022Article
- Targeting Notch to Maximize Chemotherapeutic Benefits: Rationale, Advanced Strategies, and Future Perspectives.Cancers · 2021Review
- Review
- Review
Corrections and comments
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Authors and funding
18 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Unfolded protein response (UPR) is a conserved adaptive response that tries to restore protein homeostasis after endoplasmic reticulum (ER) stress. Recent studies highlighted the role of UPR in acute leukemias and UPR targeting has been suggested as a therapeutic approach. Aberrant Notch signaling is a common feature of T-cell acute lymphoblastic leukemia (T-ALL), as downregulation of Notch activity negatively affects T-ALL cell survival, leading to the employment of Notch inhibitors in T-ALL therapy. Here we demonstrate that Notch3 is able to sustain UPR in T-ALL cells, as Notch3 silencing favored a Bip-dependent IRE1α inactivation under ER stress conditions, leading to increased apoptosis via upregulation of the ER stress cell death mediator CHOP. By using Juglone, a naturally occurring naphthoquinone acting as an anticancer agent, to decrease Notch3 expression and induce ER stress, we observed an increased ER stress-associated apoptosis. Altogether our results suggest that Notch3 inhibition may prevent leukemia cells from engaging a functional UPR needed to compensate the Juglone-mediated ER proteotoxic stress. Notably, in vivo administration of Juglone to human T-ALL xenotransplant models significantly reduced tumor growth, finally fostering the exploitation of Juglone-dependent Notch3 inhibition to perturb the ER stress/UPR signaling in Notch3-dependent T-ALL subsets.
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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.