Evidence map›Paper›PMID 27362730›Full record

ArticleBritish journal of cancer2016

Cancer cell-derived 12(S)-HETE signals via 12-HETE receptor, RHO, ROCK and MLC2 to induce lymph endothelial barrier breaching.

Chi Huu Nguyen, Serena Stadler, Stefan Brenner, Nicole Huttary, Sigurd Krieger, Walter Jäger, Helmut Dolznig, Georg Krupitza

Open access · hybridAbstract read
In one paragraph

Article in British journal of cancer, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
2.4field-weighted citation impact, top 13% 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

16 citing papers in PubMed, 37 citations in OpenAlex.

  1. Article
  2. Review
  3. Impacts of Oxylipins on ischemic stroke: from pathophysiology to clinical phenotypes.Metabolomics : Official journal of the Metabolomic Society · 2025
    Review
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  5. AFrontiers in cardiovascular medicine · 2024
    Article
  6. Review
  7. Review
  8. Lipopeptide Pepducins as Therapeutic Agents.Methods in molecular biology (Clifton, N.J.) · 2022
    Article
  9. Review
  10. Review
  11. Article
  12. Eicosanoids and cancer.Clinics (Sao Paulo, Brazil) · 2018
    Article
  13. Article
  14. Who is the real 12-HETrE?Prostaglandins & other lipid mediators · 2017
    Review
  15. Article
  16. 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

8 authors at 2 institutions in 1 country.

Chi Huu NguyenDepartment for Clinical Pharmacy and Diagnostics, Faculty of Life Sciences, University of Vienna, Althanstrasse 14, A-1090 Vienna, Austria.
Serena StadlerClinical Institute of Pathology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
Stefan BrennerDepartment for Clinical Pharmacy and Diagnostics, Faculty of Life Sciences, University of Vienna, Althanstrasse 14, A-1090 Vienna, Austria.
Nicole HuttaryClinical Institute of Pathology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
Sigurd KriegerClinical Institute of Pathology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
Walter JägerDepartment for Clinical Pharmacy and Diagnostics, Faculty of Life Sciences, University of Vienna, Althanstrasse 14, A-1090 Vienna, Austria.
Helmut DolznigInstitute of Medical Genetics, Medical University of Vienna, Waehringer Strasse 10, A-1090 Vienna, Austria.
Georg KrupitzaClinical Institute of Pathology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
Medical University of Vienna · ATUniversity of Vienna · AT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe arachidonic acid metabolite 12(S)-HETE is suspected to enhance metastatic spread by inducing cancer cell- and lymph endothelial cell (LEC) motility. However, the molecular mechanisms leading to 12(S)-HETE-triggered cell migration are still elusive.

methodsTo delineate the signalling pathways involved in 12(S)-HETE-mediated migration, inhibitors against RHO and ROCK, and specific siRNAs downregulating 12(S)-HETE receptor (12-HETER) and myosin light chain 2 (MLC2) were used. The breaching of the endothelial barrier was investigated by an assay measuring tumour spheroid-triggered 'circular chemorepellent-induced defects' (CCIDs), and respective signal transduction was elucidated by western blotting.

resultsWe provide evidence that 12(S)-HETE phosphorylated (and activated) MLC2, which regulates actin/myosin-based contraction. MLC2 activation was found to be essential for LEC retraction and CCID formation. Furthermore, we show that 12(S)-HETE activated a 12-HETER-RHO-ROCK-MYPT signalling cascade to induce MLC2 function.

conclusionsSignalling via this pathway is described for this metabolite for the first time. This may provide potential targets for the intervention of metastatic colonisation.

Indexed as

Signal Transduction12-Hydroxy-5,8,10,14-eicosatetraenoic AcidCell Line, TumorEndothelium, LymphaticHumansMyosin Light ChainsPermeabilityPhosphorylationReceptors, Eicosanoidrho-Associated KinasesRho Factor12-Hydroxy-5,8,10,14-eicosatetraenoic Acid12-hydroxyeicosatetraenoic acid receptorMyosin Light ChainsReceptors, Eicosanoidrho-Associated KinasesRho Factor

Identifiers

PMID27362730
PMCPMC4973159
OpenAlexW2471431530

What OpenQuestion holds

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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.