ArticleFrontiers in cell and developmental biology2021
Death Receptors DR4 and DR5 Undergo Spontaneous and Ligand-Mediated Endocytosis and Recycling Regardless of the Sensitivity of Cancer Cells to TRAIL.
Article in Frontiers in cell and developmental biology, 2021. 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 25 papers, 2 of them syntheses that pooled it.
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 2 syntheses or guidelines pooled it, 39 citations in OpenAlex.
- Can Environmental Enrichment Mitigate Cell Apoptosis in the Central Nervous System Under Adverse Health Conditions? A Systematic Review.Clinical and translational science · 2026Pooled it
- The role of DAPK2 as a key regulatory element in various human cancers: a systematic review.Molecular biology reports · 2024Pooled it
- Modulation of HMGB1, PRF1, TRAIL, and M-CSF after TARGIT-IORT in breast-conserving surgery: defining a unique acute immune landscape.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Article
- One-Step Microfluidic Manufactured Fucose-Decorated Sweetosomes Choose the Time and the Road for Their Intracellular Journey to Cancer Treatment.Advanced healthcare materials · 2026Article
- Orthogonal Tri-Modular Coiled-Coil Assembly for Programmable Multi-Cargo Display on Escherichia coli Nissle 1917.Small (Weinheim an der Bergstrasse, Germany) · 2026Article
- MUDENG, a component of adaptor complex 5, mediates TRAIL- and TMZ-triggered apoptosis in glioblastoma (GBM) via multiple pathways.Apoptosis : an international journal on programmed cell death · 2026Article
- Hot on the TRAIL: Targeting SPHK1 in Colorectal Cancer: Therapeutic Potential of PF-543.Digestive diseases and sciences · 2026Article
- Loss of ADAM15 prevents necroptosis induction by partial RIPK1 degradation due to enhanced TNF-R1 surface expression and basal caspase-8 activation.Cell communication and signaling : CCS · 2025Article
- Amphiphilic Poly(N-vinylpyrrolidone) Biocomposites with Bortezomib and DR5-Selective TRAIL Variants: A Promising Approach to Pancreatic Cancer Treatment.International journal of molecular sciences · 2025Article
- Quercetin Increases Expression of Membrane-TRAIL in Glioblastoma Cells Resulting in Apoptosis.Cancers · 2025Article
- The therapeutic potential of pegylated arginase I treatment in glioblastoma.Scientific reports · 2025Article
- Applying Ultrasound to Mechanically and Noninvasively Sensitize Prostate Tumors to TRAIL-Mediated Apoptosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Turn TRAIL Into Better Anticancer Therapeutic Through TRAIL Fusion Proteins.Cancer medicine · 2025Review
- From Crypts to Cancer: A Holistic Perspective on Colorectal Carcinogenesis and Therapeutic Strategies.International journal of molecular sciences · 2024Review
- Article
- The E3 ubiquitin ligase Itch regulates death receptor and cholesterol trafficking to affect TRAIL-mediated apoptosis.Cell death & disease · 2024Article
- Nimesulide, a COX-2 inhibitor, sensitizes pancreatic cancer cells to TRAIL-induced apoptosis by promoting DR5 clustering †.Cancer biology & therapy · 2023Article
- Heparan sulfate promotes TRAIL-induced tumor cell apoptosis.bioRxiv : the preprint server for biology · 2023Article
- Indirubin Inhibits TRAIL-Induced Activation of Death Receptor 5 in Jurkat Cells.Natural product communications · 2023Article
- Nano-TRAIL: a promising path to cancer therapy.Cancer drug resistance (Alhambra, Calif.) · 2023Review
Corrections and comments
- Erratum issued
Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumor necrosis factor-associated ligand inducing apoptosis (TRAIL) induces apoptosis through the death receptors (DRs) 4 and 5 expressed on the cell surface. Upon ligand stimulation, death receptors are rapidly internalized through clathrin-dependent and -independent mechanisms. However, there have been conflicting data on the role of death receptor endocytosis in apoptotic TRAIL signaling and possible cell type-specific differences in TRAIL signaling have been proposed. Here we have compared the kinetics of TRAIL-mediated internalization and subsequent recycling of DR4 and DR5 in resistant (HT-29 and A549) and sensitive (HCT116 and Jurkat) tumor cell lines of various origin. TRAIL stimulated the internalization of both receptors in a concentration-dependent manner with similar kinetics in sensitive and resistant cell lines without affecting the steady-state expression of DR4 and DR5 in cell lysates. Using the receptor-selective TRAIL variant DR5-B, we have shown that DR5 is internalized independently of DR4 receptor. After internalization and elimination of TRAIL from culture medium, the receptors slowly return to the plasma membrane. Within 4 h in resistant or 6 h in sensitive cells, the surface expression of receptors was completely restored. Recovery of receptors occurred both from newly synthesized molecules or from trans-Golgi network, as cycloheximide and brefeldin A inhibited this process. These agents also suppressed the expression of cell surface receptors in a time- and concentration-dependent manner, indicating that DRs undergo constitutive endocytosis. Inhibition of receptor endocytosis by sucrose led to sensitization of resistant cells to TRAIL and to an increase in its cytotoxic activity against sensitive cells. Our results confirm the universal nature of TRAIL-induced death receptor endocytosis, thus cell sensitivity to TRAIL can be associated with post-endocytic events.
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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.