ArticleCell death & disease2015
Inhibition of Notch1 signaling overcomes resistance to the death ligand Trail by specificity protein 1-dependent upregulation of death receptor 5.
Article in Cell death & disease, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
What it found
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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.
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Who cites it
5 citing papers in PubMed, 10 citations in OpenAlex.
- Unraveling the Complexity of Regulated Cell Death in Esophageal Cancer: from Underlying Mechanisms to Targeted Therapeutics.International journal of biological sciences · 2023Review
- Developing TRAIL/TRAIL death receptor-based cancer therapies.Cancer metastasis reviews · 2018Review
- Vemurafenib Limits Influenza A Virus Propagation by Targeting Multiple Signaling Pathways.Frontiers in microbiology · 2017Article
- Patient-derived glioblastoma stem cells respond differentially to targeted therapies.Oncotarget · 2016Article
- Inhibition of deubiquitinases primes glioblastoma cells to apoptosis in vitro and in vivo.Oncotarget · 2016Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Notch1 signaling pathway contributes to tumorigenesis by influencing differentiation, proliferation and apoptosis. Here, we demonstrate that inhibition of the Notch1 signaling pathway sensitizes glioblastoma cell lines and glioblastoma initiating cells to apoptosis induced by the death ligand TRAIL. This sensitization occurs through transcriptional upregulation of the death receptor 5 (DR5, TRAIL-R2). The increase in DR5 expression is abrogated by concomitant repression of the transcription factor Sp1, which directly binds to the DR5 promoter in the absence of Notch1 as revealed by chromatin immunoprecipitation. Consistent with these findings, Notch1 inhibition resulted in increased DR5 promoter activity, which was impaired by mutation of one out of two Sp1-binding sites within the proximal DR5 promoter. Moreover, we demonstrate that JNK signaling contributes to the regulation of DR5 expression by Notch1. Taken together, our results identify Notch1 as key driver for TRAIL resistance and suggest Notch1 as a promising target for anti-glioblastoma therapy.
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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.