ArticlePloS one2013
Sensitivity of malignant peripheral nerve sheath tumor cells to TRAIL is augmented by loss of NF1 through modulation of MYC/MAD and is potentiated by curcumin through induction of ROS.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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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
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.
- Multifunctionality of Calebin A in inflammation, chronic diseases and cancer.Frontiers in oncology · 2022Pooled it
- Untangling the Role of MYC in Sarcomas and Its Potential as a Promising Therapeutic Target.International journal of molecular sciences · 2025Review
- The Contribution of Oxidative Stress toAntioxidants (Basel, Switzerland) · 2023Review
- Review
- The Role of ER Stress-Related Phenomena in the Biology of Malignant Peripheral Nerve Sheath Tumors.International journal of molecular sciences · 2021Review
- Chromosome 8 gain is associated with high-grade transformation in MPNST.JCI insight · 2021Article
- Combined Targeting of AKT and mTOR Inhibits Proliferation of Human NF1-Associated Malignant Peripheral Nerve Sheath Tumour Cells In Vitro but not in a Xenograft Mouse Model In Vivo.International journal of molecular sciences · 2020Article
- Feasibility of using NF1-GRD and AAV for gene replacement therapy in NF1-associated tumors.Gene therapy · 2019Article
- New Molecular Mechanism Underlying Myc-Mediated Cytochrome P450 2E1 Upregulation in Apoptosis and Energy Metabolism in the Myocardium.Journal of the American Heart Association · 2019Article
- Ciprofloxacin Enhances TRAIL-Induced Apoptosis in Lung Cancer Cells by Upregulating the Expression and Protein Stability of Death Receptors through CHOP Expression.International journal of molecular sciences · 2018Article
- Targeted inhibition of glutaminase as a potential new approach for the treatment ofOncotarget · 2017Article
- Article
- Article
- [Thioridazine Sensitizes Apoptotic Effect of TRAIL in Human Lung Cancer PC9 Cells Through ER Stress Mediated Up-regulation of DR5].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2017Article
- Effects of High Glucose on Cell Viability and Differentiation in Primary Cultured Schwann Cells: Potential Role of ERK Signaling Pathway.Neurochemical research · 2016Article
- Article
- Curcumin: a double hit on malignant mesothelioma.Cancer prevention research (Philadelphia, Pa.) · 2014Article
- Capilliposide Isolated from Lysimachia capillipes Hemsl. Induces ROS Generation, Cell Cycle Arrest, and Apoptosis in Human Nonsmall Cell Lung Cancer Cell Lines.Evidence-based complementary and alternative medicine : eCAM · 2014Article
- Loss of connective tissue growth factor as an unfavorable prognosis factor activates miR-18b by PI3K/AKT/C-Jun and C-Myc and promotes cell growth in nasopharyngeal carcinoma.Cell death & disease · 2013Article
- Curcuma Contra Cancer? Curcumin and Hodgkin's Lymphoma.Cancer growth and metastasis · 2013Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Malignant peripheral nerve sheath tumor (MPNST) is a rare aggressive form of sarcoma often associated with the tumor syndrome neurofibromatosis type 1 (NF1). We investigated the effects of tumor necrosis factor-related apoptosis inducing ligand (TRAIL) on NF1 associated MPNST and determinants of TRAIL sensitivity. MPNST cell lines with complete neurofibromin deficiency were sensitive to apoptotic cell death induced by TRAIL whereas MPNST cells with retained neurofibromin expression or normal human Schwann cells were resistant. Increased sensitivity to TRAIL was associated with overexpression of death receptors, especially DR5. Re-expression of the GAP related domain of neurofibromin (NF1-GRD) suppressed DR5 expression and decreased sensitivity to TRAIL. We show that death receptor expression and TRAIL sensitivity critically depend on c-MYC and that c-MYC amounts are increased by MEK/ERK and PI3K/AKT signalling pathways which are suppressed by neurofibromin. Furthermore PI3K/AKT signalling strongly suppresses the MYC-antagonist MAD1 which significantly contributes to TRAIL sensitivity. Re-expression of the NF1-GRD decreased c-MYC and increased MAD1 amounts suggesting that neurofibromin influences TRAIL sensitivity at least in part by modulating the MYC/MAX/MAD network. The phytochemical curcumin further increased the sensitivity of neurofibromin deficient MPNST cells to TRAIL. This was presumably mediated by ROS, as it correlated with increased ROS production, was blocked by N-acetylcysteine and mimicked by exogenous ROS.
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