Evidence map›Paper›PMID 22593214›Full record

ArticleMolecular biology of the cell2012

Microtubules regulate GEF-H1 in response to extracellular matrix stiffness.

Jessica N Heck, Suzanne M Ponik, Maria G Garcia-Mendoza, Carolyn A Pehlke, David R Inman, Kevin W Eliceiri, Patricia J Keely

Abstract read
In one paragraph

Article in Molecular biology of the cell, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
69citing papers in PubMed, 1 pooled it
3.4field-weighted citation impact, top 7% 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

69 citing papers in PubMed, 1 synthesis or guideline pooled it, 92 citations in OpenAlex.

  1. Pooled it
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  17. Insulin secretion hot spots in pancreatic β cells as secreting adhesions.Frontiers in cell and developmental biology · 2023
    Article
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  19. Article
  20. Article

9 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

7 authors at 1 institution in 1 country.

Jessica N HeckDepartment of Cell and Regenerative Biology, University of Wisconsin, Madison, WI 53706, USA. heck@wisc.edu
Suzanne M Ponik
Maria G Garcia-Mendoza
Carolyn A Pehlke
David R Inman
Kevin W Eliceiri
Patricia J Keely
University of Wisconsin–Madison · US

Funding

UW COMPREHENSIVE CANCER CENTER SUPPORTP30CA014520 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI AMY TRENTHAM-DIETZ · 1985 to 2026
$142.6M
Research Training for Computation and Informatics in Biology and MedicineT15LM007359 · NLM · UNIVERSITY OF WISCONSIN-MADISON · PI Mark W. Craven, Colin Noel Dewey · 2002 to 2026
$22.6M
Training Program In Molecular AND Cellular PharmacologyT32GM008688 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI AUDHYA, ANJON · 1998 to 2020
$6.0M
Mechanisms Of Cell Migration On 3D Aligned MatricesR01CA142833 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI FRIEDL, ANDREAS, HAHN, KLAUS M. · 2010 to 2020
$3.4M
Biophysical Regulation of Breast DifferentiationR01CA114462 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI KEELY, PATRICIA J · 2010 to 2014
$1.5M
NCI NIH HHS P30 CA014520NCI NIH HHS R01 CA114462NCI NIH HHS R01 CA142833NIGMS NIH HHS T32 GM008688NLM NIH HHS 5T15LM007359NLM NIH HHS T15 LM007359
6 · The paper itself

Abstract

Breast epithelial cells sense the stiffness of the extracellular matrix through Rho-mediated contractility. In turn, matrix stiffness regulates RhoA activity. However, the upstream signaling mechanisms are poorly defined. Here we demonstrate that the Rho exchange factor GEF-H1 mediates RhoA activation in response to extracellular matrix stiffness. We demonstrate the novel finding that microtubule stability is diminished by a stiff three-dimensional (3D) extracellular matrix, which leads to the activation of GEF-H1. Surprisingly, activation of the mitogen-activated protein kinase kinase/extracellular signal-regulated kinase pathway did not contribute to stiffness-induced GEF-H1 activation. Loss of GEF-H1 decreases cell contraction of and invasion through 3D matrices. These data support a model in which matrix stiffness regulates RhoA through microtubule destabilization and the subsequent release and activation of GEF-H1.

Indexed as

AnimalsBiomechanical PhenomenaCell MovementCells, CulturedEpithelial CellsExtracellular MatrixExtracellular Signal-Regulated MAP KinasesGene Knockdown TechniquesGuanine Nucleotide Exchange FactorsHumansMammary Glands, AnimalMAP Kinase Signaling SystemMiceMicrotubulesProtein StabilityrhoA GTP-Binding ProteinARHGEF2 protein, humanExtracellular Signal-Regulated MAP KinasesGuanine Nucleotide Exchange FactorsrhoA GTP-Binding ProteinRHOA protein, humanRho Guanine Nucleotide Exchange Factors

Identifiers

PMID22593214
PMCPMC3386221
OpenAlexW2160532246

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.