ArticlePloS one2019
Impact of p53 status on TRAIL-mediated apoptotic and non-apoptotic signaling in cancer cells.
Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 50 citations in OpenAlex.
- TRAIL splice variant TRAILshort disrupts T cell receptor signaling and promotes immune tolerance in vivo.The Journal of clinical investigation · 2026Article
- Curcumin enhances the effects of TRAIL in TRAIL-resistant non-small cell lung cancer cell lines.BMC complementary medicine and therapies · 2026Article
- The SERPINB4 gene mutation identified in twin patients with Crohn's disease impaires the intestinal epithelial cell functions.Scientific reports · 2025Article
- 4-Furanylvinylquinoline derivative as a new scaffold for the design of oxidative stress initiator and glucose transporter inhibitor drugs.Scientific reports · 2024Article
- Article
- IL-8 and PI3K pathway influence the susceptibility of TRAIL-sensitive colorectal cancer cells to TRAIL-induced cell death.Molecular biology reports · 2024Article
- An interpretable machine learning-based cerebrospinal fluid proteomics clock for predicting age reveals novel insights into brain aging.Aging cell · 2024Article
- Multiple mechanisms contribute to acquired TRAIL resistance in multiple myeloma.Cancer cell international · 2024Article
- Review
- Review
- TRAIL-Sensitizing Effects of Flavonoids in Cancer.International journal of molecular sciences · 2023Review
- Design, synthesis, in vitro anticancer, molecular docking and SAR studies of new series of pyrrolo[2,3-d]pyrimidine derivatives.BMC chemistry · 2023Article
- Exosomal delivery of TRAIL and miR‑335 for the treatment of hepatocellular carcinoma (Review).International journal of molecular medicine · 2023Review
- Combined Drug Targeting of p53-dependent and -independent Pathways Depletes Myelofibrosis Hematopoietic Stem/Progenitor Cells.Leukemia · 2022Article
- Artemisinin-Type Drugs in Tumor Cell Death: Mechanisms, Combination Treatment with Biologics and Nanoparticle Delivery.Pharmaceutics · 2022Review
- New Approach about the Signaling Crosstalk between IQGAPs/ NF- κB/IL-8 and PDCD5/p53/TRAIL Pathways that Modulate Malignant Transformation in Hepatocellular Carcinoma.Asian Pacific journal of cancer prevention : APJCP · 2022Article
- BH3-only protein expression determines hepatocellular carcinoma response to sorafenib-based treatment.Cell death & disease · 2021Article
- LncRNA AC079630.4 expression associated with the progression and prognosis in lung cancer.Aging · 2021Article
- lncRNA WT1-AS is upregulated in osteoporosis and regulates the apoptosis of osteoblasts by interacting with p53.Experimental and therapeutic medicine · 2021Article
- The TRAIL in the Treatment of Human Cancer: An Update on Clinical Trials.Frontiers in molecular biosciences · 2021Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Due to their ability to preferentially induce cell death in tumor cells, while sparing healthy cells, TNF-related apoptosis-inducing ligand (TRAIL) and agonistic anti-TRAIL-R1 or anti-TRAIL-R2-specific antibodies are under clinical investigations for cancer-treatment. However, TRAIL-Rs may also induce signaling pathways, which result in malignant progression. TRAIL receptors are transcriptionally upregulated via wild-type p53 following radio- or chemotherapy. Nevertheless, the impact of p53 status on the expression and signaling of TRAIL-Rs is not fully understood. Therefore, we analyzed side by side apoptotic and non-apoptotic signaling induced by TRAIL or the agonistic TRAIL-R-specific antibodies Mapatumumab (anti-TRAIL-R1) and Lexatumumab (anti-TRAIL-R2) in the two isogenic colon carcinoma cell lines HCT116 p53+/+ and p53-/-. We found that HCT116 p53+/+ cells were significantly more sensitive to TRAIL-R-triggering than p53-/- cells. Similarly, A549 lung cancer cells expressing wild-type p53 were more sensitive to TRAIL-R-mediated cell death than their derivatives with knockdown of p53. Our data demonstrate that the contribution of p53 in regulating TRAIL-R-induced apoptosis does not correlate to the levels of TRAIL-Rs at the plasma membrane, but rather to p53-mediated upregulation of Bax, favouring the mitochondrial amplification loop. Consistently, stronger caspase-9 and caspase-3 activation as well as PARP-cleavage was observed following TRAIL-R-triggering in HCT116 p53+/+ compared to HCT116 p53-/- cells. Interestingly, HCT116 p53+/+ cells showed also a more potent activation of non-canonical TRAIL-R-induced signal transduction pathways like JNK, p38 and ERK1/ERK2 than p53-/- cells. Likewise, these cells induced IL-8 expression in response to TRAIL, Mapatumumab or Lexatumumab significantly stronger than p53-/- cells. We obtained similar results in A549 cells with or without p53-knockdown and in the two isogenic colon cancer cell lines RKO p53+/+ and p53-/-. In both cellular systems, we could clearly demonstrate the potentiating effects of p53 on TRAIL-R-mediated IL-8 induction. In conclusion, we found that wild-type p53 increases TRAIL-R-mediated apoptosis but simultaneously augments non-apoptotic signaling.
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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.