Evidence map›Paper›PMID 27821809›Full record

ArticleOncotarget2016

TRAIL induces pro-apoptotic crosstalk between the TRAIL-receptor signaling pathway and TrkAIII in SH-SY5Y cells, unveiling a potential therapeutic "Achilles heel" for the TrkAIII oncoprotein in neuroblastoma.

Luciana Gneo, Pierdomenico Ruggeri, Lucia Cappabianca, Antonietta Rosella Farina, Natalia Di Ianni, Andrew Reay Mackay

Open access · diamondAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
0.7field-weighted citation impact, top 25% 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

10 citing papers in PubMed, 8 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Review
  6. Hypoxia-induced alternative splicing: the 11th Hallmark of Cancer.Journal of experimental & clinical cancer research : CR · 2020
    Review
  7. Article
  8. The oncogenic neurotrophin receptor tropomyosin-related kinase variant, TrkAIII.Journal of experimental & clinical cancer research : CR · 2018
    Review
  9. Article
  10. Article
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 1 institution in 1 country.

Luciana GneoDepartment of Applied Clinical and Biotechnological Sciences, University of L'Aquila, L'Aquila 67100, Italy.
Pierdomenico RuggeriDepartment of Applied Clinical and Biotechnological Sciences, University of L'Aquila, L'Aquila 67100, Italy.
Lucia CappabiancaDepartment of Applied Clinical and Biotechnological Sciences, University of L'Aquila, L'Aquila 67100, Italy.
Antonietta Rosella FarinaDepartment of Applied Clinical and Biotechnological Sciences, University of L'Aquila, L'Aquila 67100, Italy.
Natalia Di IanniDepartment of Applied Clinical and Biotechnological Sciences, University of L'Aquila, L'Aquila 67100, Italy.
Andrew Reay MackayDepartment of Applied Clinical and Biotechnological Sciences, University of L'Aquila, L'Aquila 67100, Italy.
University of L'Aquila · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

TrkAIII expression in neuroblastoma (NB) associates with advanced stage disease, worse prognosis, post therapeutic relapse, and in NB models TrkAIII exhibits oncogenic activity and promotes chemotherapeutic-resistance. Here, we report a potential therapeutic "Achilles heel" for the TrkAIII oncoprotein in a SH-SY5Y NB model that is characterised by one-way TRAIL-induced, pro-apoptotic crosstalk between the TRAIL receptor signaling pathway and TrkAIII that results in the delayed induction of apoptosis. In TrkAIII SH-SY5Y cells, blocked in the intrinsic apoptosis pathway by elevated constitutive Bcl-2, Bcl-xL and Mcl-1 expression, TRAIL induced delayed caspase-dependent apoptosis via the extrinsic pathway and completely abrogated tumourigenic capacity in vitro. This effect was initiated by TRAIL-induced SHP-dependent c-Src activation, the induction of TrkAIII/SHP-1/c-Src complexing leading to SHP-mediated TrkAIII de-phosphorylation, subsequent induction of complexing between de-phosphorylated TrkAIII and cFLIP associated with a time-dependent increase the caspase-8 to cFLIP ratio at activated death receptors, resulting in delayed caspase cleavage and caspase-dependent apoptosis. We also confirm rate-limiting roles for c-FLIP and Mcl-1 in regulating the sensitivity of TrkAIII SH-SY5Y cells to TRAIL-induced apoptosis via the extrinsic and intrinsic pathways, respectively. Our study unveils a novel mechanism for the TRAIL-induced apoptosis of TrkAIII expressing NB cells that depends upon SHP/Src-mediated crosstalk between the TRAIL-receptor signaling pathway and TrkAIII, and supports a novel potential pro-apoptotic therapeutic use for TRAIL in TrkAIII expressing NB.

Indexed as

Drug Resistance, NeoplasmReceptor Cross-TalkAntineoplastic AgentsApoptosisApoptosis Regulatory ProteinsCell Line, TumorDose-Response Relationship, DrugHumansNeuroblastomaPhosphorylationProtein Tyrosine Phosphatases, Non-ReceptorReceptors, TNF-Related Apoptosis-Inducing LigandReceptor, trkARNA InterferenceSignal Transductionsrc-Family KinasesAntineoplastic AgentsApoptosis Regulatory ProteinsNTRK1 protein, humanProtein Tyrosine Phosphatases, Non-ReceptorReceptors, TNF-Related Apoptosis-Inducing LigandReceptor, trkAsrc-Family KinasesTNF-Related Apoptosis-Inducing LigandTNFSF10 protein, humanapoptosisneuroblastomaSH-SY5YTRAILTrkAIII oncoprotein

Identifiers

PMID27821809
PMCPMC5348358
OpenAlexW2547074420

What OpenQuestion holds

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Registered trials

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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.