Evidence map›Paper›PMID 31243273›Full record

ArticleNature communications2019

Switch-like enhancement of epithelial-mesenchymal transition by YAP through feedback regulation of WT1 and Rho-family GTPases.

JinSeok Park, Deok-Ho Kim, Sagar R Shah, Hong-Nam Kim, Kshitiz, Peter Kim, Alfredo Quiñones-Hinojosa, Andre Levchenko

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers.

0numbers the graph read from it
0cells of the map it votes in
86citing papers in PubMed
8.9field-weighted citation impact, top 1% 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

86 citing papers in PubMed, 124 citations in OpenAlex.

  1. Article
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  8. Identification of PKN2 and MOB4 as Coordinators of Collective Cell Migration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
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  16. Systems Biology of the Cancer Cell.Annual review of biomedical engineering · 2025
    Review
  17. Article
  18. Article
  19. Article
  20. Article

26 more citing papers are in PubMed but not listed here.

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 5 institutions in 3 countries.

JinSeok ParkDepartment of Biomedical Engineering and Yale Systems Biology Institute, Yale University, New Haven, CT, 06520, USA.
Deok-Ho KimDepartment of Bioengineering and Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, 98195, USA.
Sagar R ShahDepartment of Biomedical Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA.
Hong-Nam KimCenter for BioMicrosystems, Korea Institute of Science and Technology, Seoul, 02792, Republic of Korea.
KshitizDepartment of Biomedical Engineering and Yale Systems Biology Institute, Yale University, New Haven, CT, 06520, USA.
Peter KimDepartment of Bioengineering and Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, 98195, USA.
Alfredo Quiñones-HinojosaDepartment of Neurologic Surgery, Mayo Clinic, Jacksonville, FL, 32224, USA. Quinones-Hinojosa.Alfredo@mayo.edu.
Andre LevchenkoDepartment of Biomedical Engineering and Yale Systems Biology Institute, Yale University, New Haven, CT, 06520, USA. andre.levchenko@yale.edu.ORCID http://orcid.org/0000-0001-6262-1222
Yale University · USUniversity of Washington · USJacksonville College · USJohns Hopkins University · USKorea Institute of Science and Technology · KR

Funding

Translational Bioimaging Core Shared ResourceP30CA015704 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Eric Collisson · 1985 to 2026
$296.4M
Systems analysis of phenotypic switch in control of cancer invasionU54CA209992 · NCI · YALE UNIVERSITY · PI LEVCHENKO, ANDRE · 2016 to 2021
$10.1M
Role of NKCC1 on Brain Tumor Stem Cell Migration After EGF and Slit-2 StimulationR01NS070024 · NINDS · JOHNS HOPKINS UNIVERSITY · PI QUINONES-HINOJOSA, ALFREDO · 2010 to 2014
$2.4M
Analysis of the Signaling and Mechanical Cues Promoting Invasion in MelanomaU01CA155758 · NCI · YALE UNIVERSITY · PI LAUFFENBURGER, DOUGLAS A, LEVCHENKO, ANDRE · 2011 to 2015
$1.8M
A Nanopatterned Interdigitated Electrode Array Device for Anti-migratory Cancer Drug ScreeningR43CA221659 · NCI · CURI BIO INC · PI GEISSE, NICHOLAS ANDREW · 2017 to 2017
$225k
NCI NIH HHS P30 CA015704NCI NIH HHS R43 CA221659NCI NIH HHS U01 CA155758NCI NIH HHS U54 CA209992NINDS NIH HHS R01 NS070024U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) P30CA015704U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R43CA221659U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) U01CA155758U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) U54CA209992
6 · The paper itself

Abstract

Collective cell migration occurs in many patho-physiological states, including wound healing and invasive cancer growth. The integrity of the expanding epithelial sheets depends on extracellular cues, including cell-cell and cell-matrix interactions. We show that the nano-scale topography of the extracellular matrix underlying epithelial cell layers can strongly affect the speed and morphology of the fronts of the expanding sheet, triggering partial and complete epithelial-mesenchymal transitions (EMTs). We further demonstrate that this behavior depends on the mechano-sensitivity of the transcription regulator YAP and two new YAP-mediated cross-regulating feedback mechanisms: Wilms Tumor-1-YAP-mediated downregulation of E-cadherin, loosening cell-cell contacts, and YAP-TRIO-Merlin mediated regulation of Rho GTPase family proteins, enhancing cell migration. These YAP-dependent feedback loops result in a switch-like change in the signaling and the expression of EMT-related markers, leading to a robust enhancement in invasive cell spread, which may lead to a worsened clinical outcome in renal and other cancers.

Indexed as

NanostructuresAdaptor Proteins, Signal TransducingAnimalsDogsEpithelial CellsEpithelial-Mesenchymal TransitionGene Knockdown TechniquesGreen Fluorescent ProteinsMadin Darby Canine Kidney Cellsrho GTP-Binding ProteinsSurface PropertiesWT1 ProteinsAdaptor Proteins, Signal TransducingGreen Fluorescent Proteinsrho GTP-Binding ProteinsWT1 Proteins

Identifiers

PMID31243273
PMCPMC6594963
OpenAlexW2963973147

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.