ArticleCell death discovery2019
Sustained NF-κB-STAT3 signaling promotes resistance to Smac mimetics in Glioma stem-like cells but creates a vulnerability to EZH2 inhibition.
Article in Cell death discovery, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 18 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 27 citations in OpenAlex.
- The Pivotal Role of NF-κB in Glioblastoma: Mechanisms of Activation and Therapeutic Implications.International journal of molecular sciences · 2025Review
- Cell death in glioblastoma and the central nervous system.Cellular oncology (Dordrecht, Netherlands) · 2025Review
- Co-evolution of glioma and immune microenvironment.Journal for immunotherapy of cancer · 2024Review
- Astrocytes and the tumor microenvironment inflammatory state dictate the killing of glioblastoma cells by Smac mimetic compounds.Cell death & disease · 2024Article
- Microfluidic-Derived Docosahexaenoic Acid Liposomes for Targeting Glioblastoma and Its Inflammatory Microenvironment.ACS applied materials & interfaces · 2024Article
- Versatile function of NF-ĸB in inflammation and cancer.Experimental hematology & oncology · 2024Review
- Deciphering the role of transcription factors in glioblastoma cancer stem cells.Acta biochimica et biophysica Sinica · 2024Review
- LncRNA-PVT1 was identified as a key regulator for TMZ resistance and STAT-related pathway in glioma.BMC cancer · 2023Article
- Evaluation of an EZH2 inhibitor in patient-derived orthotopic xenograft models of pediatric brain tumors alone and in combination with chemo- and radiation therapies.Laboratory investigation; a journal of technical methods and pathology · 2022Article
- HIF1α/HIF2α induces glioma cell dedifferentiation into cancer stem cells through Sox2 under hypoxic conditions.Journal of Cancer · 2022Article
- Review
- IGFBP2 Is a Potential Master Regulator Driving the Dysregulated Gene Network Responsible for Short Survival in Glioblastoma Multiforme.Frontiers in genetics · 2021Article
- Extracellular Vesicles Induce Mesenchymal Transition and Therapeutic Resistance in Glioblastomas through NF-κB/STAT3 Signaling.Advanced biosystems · 2020Article
- miR-525-5p Modulates Proliferation and Epithelial-Mesenchymal Transition of Glioma by Targeting Stat-1.OncoTargets and therapy · 2020Article
- Suppression of Esophageal Cancer Stem-like Cells by SNX-2112 Is Enhanced by STAT3 Silencing.Frontiers in pharmacology · 2020Article
- Review
- A TNF-NF-κB-STAT3 loop triggers resistance of glioma-stem-like cells to Smac mimetics while sensitizing to EZH2 inhibitors.Cell death & disease · 2019Article
- The STAT3 inhibitor Stattic acts independently of STAT3 to decrease histone acetylation and modulate gene expression.The Journal of biological chemistryArticle
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Glioblastoma is an incurable and highly aggressive brain tumor. Understanding therapeutic resistance and survival mechanisms driving this tumor type is key to finding effective therapies. Smac mimetics (SM) emerged as attractive cancer therapeutics particularly for tumor populations that are highly resistant to conventional apoptosis-inducing therapies. We evaluated the therapeutic efficacy of SM on Glioma stem-like cells (GSCs) and showed that this family of compounds stimulates an adaptive response triggered by TNFα. Increased expression of TNFα results in a prolonged and sustained activation of NF-κB and STAT3 signaling thus activating several tumor cell resistance mechanisms in GSCs. We show that STAT3 activation is contingent on EZH2 activation and uncover a synergistic lethality between SM and EZH2 inhibitors. Therapeutic inhibition of EZH2 impaired the viability of SM-treated GSCs. Our study outlines the molecular underpinnings of SM resistance in glioblastoma and provides mechanistic insight to overcome this resistance and increase therapeutic efficacy.
Identifiers
What OpenQuestion holds
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.