ArticleBritish journal of cancer2014
Differential response of head and neck cancer cell lines to TRAIL or Smac mimetics is associated with the cellular levels and activity of caspase-8 and caspase-10.
Article in British journal of cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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The trial behind it
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Who cites it
20 citing papers in PubMed, 25 citations in OpenAlex.
- b-AP15 enhances TRAIL-induced cell death in HNSCC via the induction of ROS/JNK/DR5 signalling.Cancer gene therapy · 2026Article
- Multifaceted Evaluation of Inhibitors of Anti-Apoptotic Proteins in Head and Neck Cancer: Insights from In Vitro, In Vivo, and Clinical Studies (Review).Pharmaceuticals (Basel, Switzerland) · 2024Review
- Mechanisms underlying reversed TRAIL sensitivity in acquired bortezomib-resistant non-small cell lung cancer cells.Cancer drug resistance (Alhambra, Calif.) · 2024Article
- Human Umbilical Cord MSC Delivered-Soluble TRAIL Inhibits the Proliferation and Promotes Apoptosis of B-ALL Cell In Vitro and In Vivo.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Exploring the Roles of HERC2 and the NEDD4L HECT E3 Ubiquitin Ligase Subfamily in p53 Signaling and the DNA Damage Response.Frontiers in oncology · 2021Review
- Major Molecular Signaling Pathways in Oral Cancer Associated With Therapeutic Resistance.Frontiers in oral health · 2020Review
- Dual Antagonist of cIAP/XIAP ASTX660 Sensitizes HPVClinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
- Novel Apoptosis-Inducing Agents for the Treatment of Cancer, a New Arsenal in the Toolbox.Cancers · 2019Review
- Targeting the BIR Domains of Inhibitor of Apoptosis (IAP) Proteins in Cancer Treatment.Computational and structural biotechnology journal · 2019Review
- MicroRNA-9 inhibits growth and invasion of head and neck cancer cells and is a predictive biomarker of response to plerixafor, an inhibitor of its target CXCR4.Molecular oncology · 2018Article
- Inhibition of mTORC2 enhances UVB-induced apoptosis in keratinocytes through a mechanism dependent on the FOXO3a transcriptional target NOXA but independent of TRAIL.Cellular signalling · 2018Article
- Systemic network analysis identifies XIAP and IκBα as potential drug targets in TRAIL resistant BRAF mutated melanoma.NPJ systems biology and applications · 2018Article
- MicroRNA-21 inhibits mitochondria-mediated apoptosis in keloid.Oncotarget · 2017Article
- Therapeutic Small Molecules Target Inhibitor of Apoptosis Proteins in Cancers with Deregulation of Extrinsic and Intrinsic Cell Death Pathways.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Review
- Cytotoxic effects of SMAC-mimetic compound LCL161 in head and neck cancer cell lines.Clinical oral investigations · 2016Article
- SMAC Mimetic Birinapant plus Radiation Eradicates Human Head and Neck Cancers with Genomic Amplifications of Cell Death Genes FADD and BIRC2.Cancer research · 2016Article
- 2-DG-Regulated RIP and c-FLIP Effect on Liver Cancer Cell Apoptosis Induced by TRAIL.Medical science monitor : international medical journal of experimental and clinical research · 2015Article
- Caspase-8 activation by TRAIL monotherapy predicts responses to IAPi and TRAIL combination treatment in breast cancer cell lines.Cell death & disease · 2015Article
- Protective effect of RIP and c-FLIP in preventing liver cancer cell apoptosis induced by TRAIL.International journal of clinical and experimental pathology · 2015Article
- Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCurrent treatment strategies for head and neck cancer are associated with significant morbidity and up to 50% of patients relapse, highlighting the need for more specific and effective therapeutics. Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) and Smac mimetics (SMs) are promising anticancer agents, but their effect on head and neck squamous cell carcinoma (HNSCC) remains unknown.
methodsWe examined the response of a panel of nine HNSCC cell lines to TRAIL and SMs and investigated the mechanism of cell type-specific response by functional analysis.
resultsHead and neck cancer cell lines revealed a converse response pattern with three cell lines being highly sensitive to Smac-164 (SM) but resistant to TRAIL, whereas the other six were sensitive to TRAIL but resistant to SM. Distinct protein expression and activation patterns were found to be associated with susceptibility of HNSCC cell lines to TRAIL and SM. Tumour necrosis factor-related apoptosis-inducing ligand sensitivity was associated with high caspase-8 and Bid protein levels, and TRAIL-sensitive cell lines were killed via the type II extrinsic apoptotic pathway. Smac mimetic-sensitive cells expressed low levels of caspase-8 and Bid but had high TNF-α expression. Smac mimetic-induced cell death was associated with caspase-10 activation, suggesting that in the absence of caspase-8, caspase-10 mediates response to SM. Cotreatment with TNF-α sensitised the resistant cells to SM, demonstrating a decisive role for TNF-α-driven feedback loop in SM sensitivity.
conclusionsTumour necrosis factor-related apoptosis-inducing ligand and SMs effectively kill HNSCC cell lines and therefore represent potential targeted therapeutics for head and neck cancer. Distinct molecular mechanisms determine the sensitivity to each agent, with levels of TNF-α, caspase-8, Bid and caspase-10 providing important predictive biomarkers of response to these agents.
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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.