ArticleBrain pathology (Zurich, Switzerland)2016
Targeting Notch Signaling and Autophagy Increases Cytotoxicity in Glioblastoma Neurospheres.
Article in Brain pathology (Zurich, Switzerland), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
28 citing papers in PubMed, 50 citations in OpenAlex.
- Role of glioma stem cells in promoting tumor chemo- and radioresistance: A systematic review of potential targeted treatments.World journal of stem cells · 2024Article
- Mechanism of Notch Signaling Pathway in Malignant Progression of Glioblastoma and Targeted Therapy.Biomolecules · 2024Review
- Influence of copper(I) nicotinate complex on the Notch1 signaling pathway in triple negative breast cancer cell lines.Scientific reports · 2024Article
- Cdk4 Regulates Glioblastoma Cell Invasion and Stemness and Is Target of a Notch Inhibitor Plus Resveratrol Combined Treatment.International journal of molecular sciences · 2023Article
- N-acetylcysteine improves autism-like behavior by recovering autophagic deficiency and decreasing Notch-1/Hes-1 pathway activity.Experimental biology and medicine (Maywood, N.J.) · 2023Article
- The Notch pathway regulates autophagy after hypoxic-ischemic injury and affects synaptic plasticity.Brain structure & function · 2023Article
- Autophagy, molecular chaperones, and unfolded protein response as promoters of tumor recurrence.Cancer metastasis reviews · 2023Review
- The interaction between autophagy and the epithelial-mesenchymal transition mediated by NICD/ULK1 is involved in the formation of diabetic cataracts.Molecular medicine (Cambridge, Mass.) · 2022Article
- Article
- The Importance of Tumor Stem Cells in Glioblastoma Resistance to Therapy.International journal of molecular sciences · 2021Review
- Unlocking the Secrets of Cancer Stem Cells with γ-Secretase Inhibitors: A Novel Anticancer Strategy.Molecules (Basel, Switzerland) · 2021Review
- A Notch inhibitor plus Resveratrol induced blockade of autophagy drives glioblastoma cell death by promoting a switch to apoptosis.American journal of cancer research · 2021Article
- A Key Pathway to Cancer Resilience: The Role of Autophagy in Glioblastomas.Frontiers in oncology · 2021Review
- Differential gene methylation and expression of HOX transcription factor family in orbitofacial neurofibroma.Acta neuropathologica communications · 2020Article
- Combination of an Autophagy Inducer and an Autophagy Inhibitor: A Smarter Strategy Emerging in Cancer Therapy.Frontiers in pharmacology · 2020Review
- The Autophagy Status of Cancer Stem Cells in Gliobastoma Multiforme: From Cancer Promotion to Therapeutic Strategies.International journal of molecular sciences · 2019Review
- Dramatic response of BRAF V600E-mutant epithelioid glioblastoma to combination therapy with BRAF and MEK inhibitor: establishment and xenograft of a cell line to predict clinical efficacy.Acta neuropathologica communications · 2019Article
- Inhibition of enhancer of zest homologue 2 is a potential therapeutic target for high-MYC medulloblastoma.Neuropathology : official journal of the Japanese Society of Neuropathology · 2019Article
- Review
- MGMT Expression Contributes to Temozolomide Resistance in H3K27M-Mutant Diffuse Midline Gliomas.Frontiers in oncology · 2019Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 4 countries.
Funding
Abstract
Glioblastomas are highly aggressive tumors that contain treatment resistant stem-like cells. Therapies targeting developmental pathways such as Notch eliminate many neoplastic glioma cells, including those with stem cell features, but their efficacy can be limited by various mechanisms. One potential avenue for chemotherapeutic resistance is the induction of autophagy, but little is known how it might modulate the response to Notch inhibitors. We used the γ-secretase inhibitor MRK003 to block Notch pathway activity in glioblastoma neurospheres and assessed its effects on autophagy. A dramatic, several fold increase of LC3B-II/LC3B-I autophagy marker was noted on western blots, along with the emergence of punctate LC3B immunostaining in cultured cells. By combining the late stage autophagy inhibitor chloroquine (CQ) with MRK003, a significant induction in apoptosis and reduction in growth was noted as compared to Notch inhibition alone. A similar beneficial effect on inhibition of cloogenicity in soft agar was seen using the combination treatment. These results demonstrated that pharmacological Notch blockade can induce protective autophagy in glioma neurospheres, resulting in chemoresistance, which can be abrogated by combination treatment with autophagy inhibitors.
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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.