Evidence map›Paper›PMID 26794130›Full record

ArticleDisease models & mechanisms2016

Phenotypic chemical screening using a zebrafish neural crest EMT reporter identifies retinoic acid as an inhibitor of epithelial morphogenesis.

Laura Jimenez, Jindong Wang, Monique A Morrison, Clifford Whatcott, Katherine K Soh, Steven Warner, David Bearss, Cicely A Jette, Rodney A Stewart

Open access · goldAbstract read
In one paragraph

Article in Disease models & mechanisms, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
2.5field-weighted citation impact, top 9% 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

18 citing papers in PubMed, 26 citations in OpenAlex.

  1. Article
  2. Review
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  4. Review
  5. Article
  6. Review
  7. Review
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  9. Review
  10. Neural crest development: insights from the zebrafish.Developmental dynamics : an official publication of the American Association of Anatomists · 2020
    Review
  11. Article
  12. Review
  13. Article
  14. Article
  15. Review
  16. Specifying neural crest cells: From chromatin to morphogens and factors in between.Wiley interdisciplinary reviews. Developmental biology · 2018
    Review
  17. Tracking neural crest cell cycle progression in vivo.Genesis (New York, N.Y. : 2000) · 2018
    Article
  18. Frontiers in oncology · 2017
    Review
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

9 authors at 3 institutions in 1 country.

Laura JimenezDepartment of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA.
Jindong WangDepartment of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA.
Monique A MorrisonDepartment of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA.
Clifford WhatcottTolero Pharmaceuticals, Inc., Lehi, UT 84043, USA.
Katherine K SohTolero Pharmaceuticals, Inc., Lehi, UT 84043, USA.
Steven WarnerTolero Pharmaceuticals, Inc., Lehi, UT 84043, USA.
David BearssTolero Pharmaceuticals, Inc., Lehi, UT 84043, USA.
Cicely A JetteDepartment of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA.
Rodney A StewartDepartment of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA Rodney.Stewart@hci.utah.edu.
Huntsman Cancer Institute · USTolero Pharmaceuticals (United States) · USUniversity of Utah · US

Funding

MULTIDISCIPLINARY CANCER RESEARCH TRAINING PROGRAMT32CA093247 · NCI · UNIVERSITY OF UTAH · PI AYER, DONALD E · 2002 to 2011
$5.2M
Neural Crest Cell Survival and Migration in ZebrafishK99NS058608 · NINDS · DANA-FARBER CANCER INST · PI STEWART, RODNEY A. · 2007 to 2008
$180k
HSRD VA CDA 13-025NCI NIH HHS 5T32CA093247NCI NIH HHS T32 CA093247NINDS NIH HHS K99 NS058608NINDS NIH HHS K99NS058608
6 · The paper itself

Abstract

The epithelial-to-mesenchymal transition (EMT) is a highly conserved morphogenetic program essential for embryogenesis, regeneration and cancer metastasis. In cancer cells, EMT also triggers cellular reprogramming and chemoresistance, which underlie disease relapse and decreased survival. Hence, identifying compounds that block EMT is essential to prevent or eradicate disseminated tumor cells. Here, we establish a whole-animal-based EMT reporter in zebrafish for rapid drug screening, calledTg(snai1b:GFP), which labels epithelial cells undergoing EMT to producesox10-positive neural crest (NC) cells. Time-lapse and lineage analysis ofTg(snai1b:GFP)embryos reveal that cranial NC cells delaminate from two regions: an early population delaminates adjacent to the neural plate, whereas a later population delaminates from within the dorsal neural tube. TreatingTg(snai1b:GFP)embryos with candidate small-molecule EMT-inhibiting compounds identified TP-0903, a multi-kinase inhibitor that blocked cranial NC cell delamination in both the lateral and medial populations. RNA sequencing (RNA-Seq) analysis and chemical rescue experiments show that TP-0903 acts through stimulating retinoic acid (RA) biosynthesis and RA-dependent transcription. These studies identify TP-0903 as a new therapeutic for activating RAin vivoand raise the possibility that RA-dependent inhibition of EMT contributes to its prior success in eliminating disseminated cancer cells.

Indexed as

Genes, ReporterAnimalsAnimals, Genetically ModifiedBenzenesulfonamidesCell DifferentiationCell MovementCell ShapeEmbryo, NonmammalianEpithelial CellsEpithelial-Mesenchymal TransitionGreen Fluorescent ProteinsMorphogenesisNeural CrestNeural TubePhenotypePyrimidinesBenzenesulfonamidesdubermatinibGreen Fluorescent ProteinsPyrimidinesSulfonamidesTretinoinZebrafish ProteinsDrug screenEMTEpithelial mesenchymalNeural crestRetinoic acidZebrafish

Identifiers

PMID26794130
PMCPMC4852498
OpenAlexW2306634928

What OpenQuestion holds

Textmetadata
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.