ArticleCell death and differentiation2011
Chemotherapy overcomes TRAIL-R4-mediated TRAIL resistance at the DISC level.
Article in Cell death and differentiation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 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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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
38 citing papers in PubMed, 82 citations in OpenAlex.
- Helping Apo2L/TRAIL in the Battle: Synergistic Therapeutic Approaches for Cancer Therapies.International journal of molecular sciences · 2026Review
- Review
- Engineered Mesenchymal Stem Cells as Treatment for Cancers: Opportunities, Clinical Applications and Challenges.The Malaysian journal of medical sciences : MJMS · 2024Review
- Article
- Review
- Interferon-β Overexpression in Adipose Tissue-Derived Stem Cells Induces HepG2 and Macrophage Cell Death in Liver Tumor Organoids via Induction of TNF-Related Apoptosis-Inducing Ligand Expression.International journal of molecular sciences · 2024Article
- Core Fucosylation Mediated by the FucT-8 Enzyme Affects TRAIL-Induced Apoptosis and Sensitivity to Chemotherapy in Human SW480 and SW620 Colorectal Cancer Cells.International journal of molecular sciences · 2023Article
- Review
- Article
- Importance of TRAIL Molecular Anatomy in Receptor Oligomerization and Signaling. Implications for Cancer Therapy.Cancers · 2019Review
- Generation and characterization of novel anti-DR4 and anti-DR5 antibodies developed by genetic immunization.Cell death & disease · 2019Article
- Review
- Regulation of TNF-Related Apoptosis-Inducing Ligand Signaling by Glycosylation.International journal of molecular sciences · 2018Review
- Autophagy as a mechanism of Apo2L/TRAIL resistance.Cancer biology & therapy · 2018Article
- The effect of cisplatin on cytotoxicity of anticancer cytokine TRAIL and its receptor-selective mutant variant DR5-BDoklady. Biochemistry and biophysics · 2017Article
- Antibodies and Derivatives Targeting DR4 and DR5 for Cancer Therapy.Antibodies (Basel, Switzerland) · 2017Review
- Improvement of Pharmacokinetic Profile of TRAIL via Trimer-Tag Enhances its Antitumor Activity in vivo.Scientific reports · 2017Article
- Overcoming chemotherapy drug resistance by targeting inhibitors of apoptosis proteins (IAPs).Apoptosis : an international journal on programmed cell death · 2017Review
- Onto better TRAILs for cancer treatment.Cell death and differentiation · 2016Review
- Selective activation of TNFR1 and NF-κB inhibition by a novel biyouyanagin analogue promotes apoptosis in acute leukemia cells.BMC cancer · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
TNF-related apoptosis-inducing ligand or Apo2L (Apo2L/TRAIL) is a promising anti-cancer drug owing to its ability to trigger apoptosis by binding to TRAIL-R1 or TRAIL-R2, two membrane-bound receptors that are often expressed by tumor cells. TRAIL can also bind non-functional receptors such as TRAIL-R4, but controversies still exist regarding their potential to inhibit TRAIL-induced apoptosis. We show here that TRAIL-R4, expressed either endogenously or ectopically, inhibits TRAIL-induced apoptosis. Interestingly, the combination of chemotherapeutic drugs with TRAIL restores tumor cell sensitivity to apoptosis in TRAIL-R4-expressing cells. This sensitization, which mainly occurs at the death-inducing signaling complex (DISC) level, through enhanced caspase-8 recruitment and activation, is compromised by c-FLIP expression and is independent of the mitochondria. Importantly, TRAIL-R4 expression prevents TRAIL-induced tumor regression in nude mice, but tumor regression induced by TRAIL can be restored with chemotherapy. Our results clearly support a negative regulatory function for TRAIL-R4 in controlling TRAIL signaling, and unveil the ability of TRAIL-R4 to cooperate with c-FLIP to inhibit TRAIL-induced cell death.
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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.