Evidence map›Paper›PMID 27008704›Full record

ArticleOncotarget2016

Stability of the hybrid epithelial/mesenchymal phenotype.

Mohit Kumar Jolly, Satyendra C Tripathi, Dongya Jia, Steven M Mooney, Muge Celiktas, Samir M Hanash, Sendurai A Mani, Kenneth J Pienta, Eshel Ben-Jacob, Herbert Levine

Open access · diamondAbstract read
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 262 papers.

0numbers the graph read from it
0cells of the map it votes in
262citing papers in PubMed
26.5field-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

262 citing papers in PubMed, 460 citations in OpenAlex.

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  8. HHIP's dynamic role in epithelial wound healing reveals a potential mechanism of COPD susceptibility.Proceedings of the National Academy of Sciences of the United States of America · 2026
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202 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

10 authors at 5 institutions in 3 countries.

Mohit Kumar JollyCenter for Theoretical Biological Physics, Rice University, Houston, TX, USA.
Satyendra C TripathiDepartment of Clinical Cancer Prevention, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Dongya JiaCenter for Theoretical Biological Physics, Rice University, Houston, TX, USA.
Steven M MooneyDepartment of Biology, University of Waterloo, Waterloo, ON, Canada.
Muge CeliktasDepartment of Clinical Cancer Prevention, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Samir M HanashDepartment of Clinical Cancer Prevention, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Sendurai A ManiDepartment of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Kenneth J PientaThe James Brady Urological Institute, and Departments of Urology, Oncology, Pharmacology and Molecular Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Eshel Ben-JacobCenter for Theoretical Biological Physics, Rice University, Houston, TX, USA.
Herbert LevineCenter for Theoretical Biological Physics, Rice University, Houston, TX, USA.
The University of Texas MD Anderson Cancer Center · USCenter for Theoretical Biological Physics · USRice University · USJohns Hopkins Medicine · USUniversity of Waterloo · CA

Funding

Tumor microvesicle-mediated modulation of the bone microenvironmentP01CA093900 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI KELLER, EVAN T · 2004 to 2024
$29.6M
TRANS_NETWORK PROJECTSU54CA143803 · NCI · PRINCETON UNIVERSITY · PI TLSTY, THEA D · 2009 to 2013
$14.2M
Pleiotropic functions of FOXC2 in EMT, stem cells and breast cancer progressionR01CA155243 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI MANI, SENDURAI AYYAVOO · 2011 to 2022
$3.2M
Mechanisms That Regulate Dormancy of Disseminated Tumor Cells in the Bone MarrowU54CA163124 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SHIOZAWA, YUSUKE · 2011 to 2015
$3.0M
Reactive Stroma and Tumor Associated Macrophages in Prostate Cancer ProgressionU01CA143055 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI PIENTA, KENNETH J., ROWLEY, DAVID R · 2010 to 2014
$2.7M
NCI NIH HHS P01 CA093900NCI NIH HHS R01 CA155243NCI NIH HHS U01 CA143055NCI NIH HHS U54 CA143803NCI NIH HHS U54 CA163124
6 · The paper itself

Abstract

Epithelial-to-Mesenchymal Transition (EMT) and its reverse - Mesenchymal to Epithelial Transition (MET) - are hallmarks of cellular plasticity during embryonic development and cancer metastasis. During EMT, epithelial cells lose cell-cell adhesion and gain migratory and invasive traits either partially or completely, leading to a hybrid epithelial/mesenchymal (hybrid E/M) or a mesenchymal phenotype respectively. Mesenchymal cells move individually, but hybrid E/M cells migrate collectively as observed during gastrulation, wound healing, and the formation of tumor clusters detected as Circulating Tumor Cells (CTCs). Typically, the hybrid E/M phenotype has largely been tacitly assumed to be transient and 'metastable'. Here, we identify certain 'phenotypic stability factors' (PSFs) such as GRHL2 that couple to the core EMT decision-making circuit (miR-200/ZEB) and stabilize hybrid E/M phenotype. Further, we show that H1975 lung cancer cells can display a stable hybrid E/M phenotype and migrate collectively, a behavior that is impaired by knockdown of GRHL2 and another previously identified PSF - OVOL. In addition, our computational model predicts that GRHL2 can also associate hybrid E/M phenotype with high tumor-initiating potential, a prediction strengthened by the observation that the higher levels of these PSFs may be predictive of poor patient outcome. Finally, based on these specific examples, we deduce certain network motifs that can stabilize the hybrid E/M phenotype. Our results suggest that partial EMT, i.e. a hybrid E/M phenotype, need not be 'metastable', and strengthen the emerging notion that partial EMT, but not necessarily a complete EMT, is associated with aggressive tumor progression.

Indexed as

Gene Expression Regulation, NeoplasticCell Line, TumorCell MovementDNA-Binding ProteinsEpithelial CellsEpithelial-Mesenchymal TransitionHumansMesenchymal Stem CellsMicroRNAsPhenotypeRNA InterferenceTranscription FactorsZinc Finger E-box-Binding Homeobox 1DNA-Binding ProteinsGRHL2 protein, humanMicroRNAsMIRN200 microRNA, humanTranscription FactorsZEB1 protein, humanZinc Finger E-box-Binding Homeobox 1cancer stem cellscell-fate decisionsepithelial-mesenchymal transitionmultistabilitypartial EMT

Identifiers

PMID27008704
PMCPMC5053633
OpenAlexW2338391827

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.