Evidence map›Paper›PMID 25143398›Full record

ArticleMolecular biology of the cell2014

TGF-β regulates LARG and GEF-H1 during EMT to affect stiffening response to force and cell invasion.

Lukas D Osborne, George Z Li, Tam How, E Tim O'Brien, Gerard C Blobe, Richard Superfine, Karthikeyan Mythreye

Abstract read
In one paragraph

Article in Molecular biology of the cell, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed, 1 pooled it
3.2field-weighted citation impact, top 8% 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

37 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.

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  15. EMT-Induced Cell-Mechanical Changes Enhance Mitotic Rounding Strength.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2020
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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

7 authors at 3 institutions in 1 country.

Lukas D OsborneDepartment of Physics and Astronomy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
George Z LiDepartment of Medicine, Duke University Medical Center, Durham, NC 27710.
Tam HowDepartment of Medicine, Duke University Medical Center, Durham, NC 27710.
E Tim O'BrienDepartment of Physics and Astronomy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
Gerard C BlobeDepartment of Medicine, Duke University Medical Center, Durham, NC 27710 karthike@mailbox.sc.edu rsuper@physics.unc.edu gerard.blobe@duke.edu.
Richard SuperfineDepartment of Physics and Astronomy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 karthike@mailbox.sc.edu rsuper@physics.unc.edu gerard.blobe@duke.edu.
Karthikeyan MythreyeDepartment of Chemistry and Biochemistry, University of South Carolina, Columbia, SC 29208 karthike@mailbox.sc.edu rsuper@physics.unc.edu gerard.blobe@duke.edu.
Duke Medical Center · USUniversity of North Carolina at Chapel Hill · USUniversity of South Carolina · US

Funding

Women's Cancer Research ProgramP30CA014236 · NCI · DUKE UNIVERSITY · PI DONNA NIEDZWIECKI · 1985 to 2026
$174.8M
INTERACTIVE GRAPHICS FOR MOLECULAR STUDIES &MICROSCOPYP41EB002025 · NIBIB · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SUPERFINE, RICHARD · 2003 to 2019
$16.9M
Role of TbRIII in Regulating Motility and InvasionR01CA135006 · NCI · DUKE UNIVERSITY · PI BLOBE, GERARD C · 2009 to 2013
$2.2M
Array Microscope Assay for Cancer Cell MechanicsR33CA155618 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SUPERFINE, RICHARD · 2011 to 2013
$939k
Howard Hughes Medical InstituteNCI NIH HHS P30 CA014236NCI NIH HHS R01 CA135006NCI NIH HHS R01-CA135006NCI NIH HHS R33 CA155618NCI NIH HHS R33-CA155618NIBIB NIH HHS P41 EB002025
6 · The paper itself

Abstract

Recent studies implicate a role for cell mechanics in cancer progression. The epithelial-to-mesenchymal transition (EMT) regulates the detachment of cancer cells from the epithelium and facilitates their invasion into stromal tissue. Although classic EMT hallmarks include loss of cell-cell adhesions, morphology changes, and increased invasion capacity, little is known about the associated mechanical changes. Previously, force application on integrins has been shown to initiate cytoskeletal rearrangements that result in increased cell stiffness and a stiffening response. Here we demonstrate that transforming growth factor β (TGF-β)-induced EMT results in decreased stiffness and loss of the normal stiffening response to force applied on integrins. We find that suppression of the RhoA guanine nucleotide exchange factors (GEFs) LARG and GEF-H1 through TGF-β/ALK5-enhanced proteasomal degradation mediates these changes in cell mechanics and affects EMT-associated invasion. Taken together, our results reveal a functional connection between attenuated stiffness and stiffening response and the increased invasion capacity acquired after TGF-β-induced EMT.

Indexed as

Gene Expression Regulation, NeoplasticAnimalsBiomechanical PhenomenaCell AdhesionCell Line, TumorCell MovementEpithelial-Mesenchymal TransitionHumansIntegrinsMechanotransduction, CellularMiceNeoplasm InvasivenessPressureRho Guanine Nucleotide Exchange FactorsTransforming Growth Factor betaARHGEF12 protein, humanARHGEF2 protein, humanIntegrinsRho Guanine Nucleotide Exchange FactorsTransforming Growth Factor beta

Identifiers

PMID25143398
PMCPMC4230614
OpenAlexW2121438179

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.