ArticleApoptosis : an international journal on programmed cell death2014
Modulation of Mcl-1 sensitizes glioblastoma to TRAIL-induced apoptosis.
Article in Apoptosis : an international journal on programmed cell death, 2014. 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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Who cites it
28 citing papers in PubMed, 47 citations in OpenAlex.
- Spatial transcriptomics of glioblastoma defines biologically and clinically significant reprogramming patterns across unique spatial microenvironments.bioRxiv : the preprint server for biology · 2025Article
- Cell death in glioblastoma and the central nervous system.Cellular oncology (Dordrecht, Netherlands) · 2025Review
- Probabilistic edge inference of gene networks with markov random field-based bayesian learning.Frontiers in genetics · 2022Article
- Article
- Overcoming TRAIL Resistance for Glioblastoma Treatment.Biomolecules · 2021Review
- Cyclin-dependent kinase inhibitors in brain cancer: current state and future directions.Cancer drug resistance (Alhambra, Calif.) · 2020Review
- Implementing Patient-Derived Xenografts to Assess the Effectiveness of Cyclin-Dependent Kinase Inhibitors in Glioblastoma.Cancers · 2019Article
- Article
- The regulatory protein GADD34 inhibits TRAIL-induced apoptosis via TRAF6/ERK-dependent stabilization of myeloid cell leukemia 1 in liver cancer cells.The Journal of biological chemistry · 2019Article
- Development of acquired resistance to lapatinib may sensitise HER2-positive breast cancer cells to apoptosis induction by obatoclax and TRAIL.BMC cancer · 2018Article
- BH3 mimetics induce apoptosis independent of DRP-1 in melanoma.Cell death & disease · 2018Article
- Article
- UMI-77 primes glioma cells for TRAIL-induced apoptosis by unsequestering Bim and Bak from Mcl-1.Molecular and cellular biochemistry · 2017Article
- Use of a MCL-1 inhibitor alone to de-bulk melanoma and in combination to kill melanoma initiating cells.Oncotarget · 2017Article
- Article
- Predicting the cell death responsiveness and sensitization of glioma cells to TRAIL and temozolomide.Oncotarget · 2016Article
- Metabolic reprogramming of glioblastoma cells by L-asparaginase sensitizes for apoptosis in vitro and in vivo.Oncotarget · 2016Article
- Inhibition of deubiquitinases primes glioblastoma cells to apoptosis in vitro and in vivo.Oncotarget · 2016Article
- Deubiquitylating enzyme USP9x regulates radiosensitivity in glioblastoma cells by Mcl-1-dependent and -independent mechanisms.Cell death & disease · 2016Article
- Resistance to Cell Death and Its Modulation in Cancer Stem Cells.Critical reviews in oncogenesis · 2016Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glioblastoma (GBM) is the most aggressive form of primary brain tumour, with dismal patient outcome. Treatment failure is associated with intrinsic or acquired apoptosis resistance and the presence of a highly tumourigenic subpopulation of cancer cells called GBM stem cells. Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) has emerged as a promising novel therapy for some treatment-resistant tumours but unfortunately GBM can be completely resistant to TRAIL monotherapy. In this study, we identified Mcl-1, an anti-apoptotic Bcl-2 family member, as a critical player involved in determining the sensitivity of GBM to TRAIL-induced apoptosis. Effective targeting of Mcl-1 in TRAIL resistant GBM cells, either by gene silencing technology or by treatment with R-roscovitine, a cyclin-dependent kinase inhibitor that targets Mcl-1, was demonstrated to augment sensitivity to TRAIL, both within GBM cells grown as monolayers and in a 3D tumour model. Finally, we highlight that two separate pathways are activated during the apoptotic death of GBM cells treated with a combination of TRAIL and R-roscovitine, one which leads to caspase-8 and caspase-3 activation and a second pathway, involving a Mcl-1:Noxa axis. In conclusion, our study demonstrates that R-roscovitine in combination with TRAIL presents a promising novel strategy to trigger cell death pathways in glioblastoma.
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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.