ArticlePloS one2011
TRAIL-R4 promotes tumor growth and resistance to apoptosis in cervical carcinoma HeLa cells through AKT.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 72 citations in OpenAlex.
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- ELF3 plays an important role in defining TRAIL sensitivity in breast cancer by modulating the expression of decoy receptor 2 (DCR2).Molecular biology reports · 2024Article
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- DPP3 expression promotes cell proliferation and migrationOncology reports · 2023Article
- Decoy receptor 2 mediates the apoptosis-resistant phenotype of senescent renal tubular cells and accelerates renal fibrosis in diabetic nephropathy.Cell death & disease · 2022Article
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- Endogenous TRAIL-R4 critically impacts apoptotic and non-apoptotic TRAIL-induced signaling in cancer cells.Frontiers in cell and developmental biology · 2022Article
- Role of Apoptosis in HIV Pathogenesis.Advances in virology · 2022Review
- Harnessing TRAIL-Induced Apoptosis Pathway for Cancer Immunotherapy and Associated Challenges.Frontiers in immunology · 2021Review
- Ischemic Preconditioning Upregulates Decoy Receptors to Protect SH-SY5Y Cells from OGD Induced Cellular Damage by Inhibiting TRAIL Pathway and Agitating PI3K/Akt Pathway.Molecular neurobiology · 2020Article
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- Survival of aging CD264Biotechnology and bioengineering · 2020Article
- Molecular Mode of Action of TRAIL Receptor Agonists-Common Principles and Their Translational Exploitation.Cancers · 2019Review
- Generation and characterization of novel anti-DR4 and anti-DR5 antibodies developed by genetic immunization.Cell death & disease · 2019Article
- Differential expression of senescence tumour markers and its implications on survival outcomes of breast cancer patients.PloS one · 2019Article
- Molecular Profiles of Cell-to-Cell Variation in the Regenerative Potential of Mesenchymal Stromal Cells.Stem cells international · 2019Review
- TRAIL-Receptor 4 Modulates γδ T Cell-Cytotoxicity Toward Cancer Cells.Frontiers in immunology · 2019Article
- Impact of p53 status on TRAIL-mediated apoptotic and non-apoptotic signaling in cancer cells.PloS one · 2019Article
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTRAIL/Apo2L is a pro-apoptotic ligand of the TNF family that engages the apoptotic machinery through two pro-apoptotic receptors, TRAIL-R1 and TRAIL-R2. This cell death program is tightly controlled by two antagonistic receptors, TRAIL-R3 and TRAIL-R4, both devoid of a functional death domain, an intracellular region of the receptor, required for the recruitment and the activation of initiator caspases. Upon TRAIL-binding, TRAIL-R4 forms a heteromeric complex with the agonistic receptor TRAIL-R2 leading to reduced caspase-8 activation and apoptosis. METHODOLOGY/PRINCIPAL
findingsWe provide evidence that TRAIL-R4 can also exhibit, in a ligand independent manner, signaling properties in the cervical carcinoma cell line HeLa, through Akt. Ectopic expression of TRAIL-R4 in HeLa cells induced morphological changes, with cell rounding, loss of adherence and markedly enhanced cell proliferation in vitro and tumor growth in vivo. Disruption of the PI3K/Akt pathway using the pharmacological inhibitor LY294002, siRNA targeting the p85 regulatory subunit of phosphatidylinositol-3 kinase, or by PTEN over-expression, partially restored TRAIL-mediated apoptosis in these cells. Moreover, the Akt inhibitor, LY294002, restituted normal cell proliferation index in HeLa cells expressing TRAIL-R4. CONCLUSIONS/SIGNIFICANCE: Altogether, these results indicate that, besides its ability to directly inhibit TRAIL-induced cell death at the membrane, TRAIL-R4 can also trigger the activation of signaling pathways leading to cell survival and proliferation in HeLa cells. Our findings raise the possibility that TRAIL-R4 may contribute to cervical carcinogenesis.
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