Evidence map›Paper›PMID 25026275›Full record

ArticleOncotarget2014

H-Ras regulation of TRAIL death receptor mediated apoptosis.

Jun-Jie Chen, William P Bozza, Xu Di, Yaqin Zhang, William Hallett, Baolin Zhang

Open access · diamondAbstract read
In one paragraph

Article in Oncotarget, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.6field-weighted citation impact, top 18% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

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.

3 · Its place in the literature

Who cites it

15 citing papers in PubMed, 20 citations in OpenAlex.

  1. Abnormal expression ofBlood research · 2023
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  2. Revealing macropinocytosis using nanoparticles.Molecular aspects of medicine · 2022
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 2 countries.

Jun-Jie ChenDivision of Therapeutic Proteins, Office of Biotechnology Products, Center for Drug Evaluation and Research, Food and Drug Administration, Bethesda, Maryland, United States; Tumor Research Laboratory, E-Da Hospital, Kaohsiung City, Taiwan.
William P BozzaDivision of Therapeutic Proteins, Office of Biotechnology Products, Center for Drug Evaluation and Research, Food and Drug Administration, Bethesda, Maryland, United States.
Xu DiDivision of Therapeutic Proteins, Office of Biotechnology Products, Center for Drug Evaluation and Research, Food and Drug Administration, Bethesda, Maryland, United States.
Yaqin ZhangDivision of Therapeutic Proteins, Office of Biotechnology Products, Center for Drug Evaluation and Research, Food and Drug Administration, Bethesda, Maryland, United States.
William HallettDivision of Therapeutic Proteins, Office of Biotechnology Products, Center for Drug Evaluation and Research, Food and Drug Administration, Bethesda, Maryland, United States.
Baolin ZhangDivision of Therapeutic Proteins, Office of Biotechnology Products, Center for Drug Evaluation and Research, Food and Drug Administration, Bethesda, Maryland, United States.
Center for Drug Evaluation and Research · USI-Shou University · TW

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

TNF-related apoptosis-inducing ligand (TRAIL) induces apoptosis through the death receptors (DRs) 4 and/or 5 expressed on the cell surface. Multiple clinical trials are underway to evaluate the antitumor activity of recombinant human TRAIL and agonistic antibodies to DR4 or DR5. However, their therapeutic potential is limited by the high frequency of cancer resistance. Here we provide evidence demonstrating the role of H-Ras in TRAIL receptor mediated apoptosis. By analyzing the genome wide mRNA expression data of the NCI60 cancer cell lines, we found that H-Ras expression was consistently upregulated in TRAIL-resistant cell lines. By contrast, no correlation was found between TRAIL sensitivity and K-Ras expression levels or their mutational profiles. Notably, H-Ras upregulation associated with a surface deficiency of TRAIL death receptors. Selective inhibition of H-Ras activity in TRAIL-resistant cells restored the surface expression of both DR4 and DR5 without changing their total protein levels. The resulting cells became highly susceptible to both TRAIL and agonistic DR5 antibody, whereas K-Ras inhibition had little or no effect on TRAIL-induced apoptosis, indicating H-Ras plays a distinct role in the regulation of TRAIL death receptors. Further studies are warranted to determine the therapeutic potential of H-Ras-specific inhibitors in combination with TRAIL receptor agonists.

Indexed as

ApoptosisApoptosis Regulatory ProteinsBlotting, WesternCell Line, TumorCell SurvivalDrug Resistance, NeoplasmGene Expression ProfilingGene Expression Regulation, NeoplasticHumansMutationNeoplasmsProto-Oncogene Proteins p21(ras)Receptors, TNF-Related Apoptosis-Inducing LigandRecombinant ProteinsReverse Transcriptase Polymerase Chain ReactionRNA InterferenceApoptosis Regulatory ProteinsHRAS protein, humanProto-Oncogene Proteins p21(ras)Receptors, TNF-Related Apoptosis-Inducing LigandRecombinant ProteinsTNF-Related Apoptosis-Inducing Ligand

Identifiers

PMID25026275
PMCPMC4148127
OpenAlexW1507358330

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.