Evidence map›Paper›PMID 25893917›Full record

ArticleNature cell biology2015

Matrix stiffness drives epithelial-mesenchymal transition and tumour metastasis through a TWIST1-G3BP2 mechanotransduction pathway.

Spencer C Wei, Laurent Fattet, Jeff H Tsai, Yurong Guo, Vincent H Pai, Hannah E Majeski, Albert C Chen, Robert L Sah, Susan S Taylor, Adam J Engler and 1 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature cell biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 561 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
561citing papers in PubMed, 1 pooled it
36.7field-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

561 citing papers in PubMed, 1 synthesis or guideline pooled it, 962 citations in OpenAlex.

  1. 3DACS biomaterials science & engineering · 2023
    Pooled it
  2. Review
  3. Review
  4. Cell plasticity in cancer and therapy resistance.Experimental & molecular medicine · 2026
    Review
  5. Review
  6. Review
  7. Review
  8. Understanding and targeting the tumour matrisome.Nature reviews. Clinical oncology · 2026
    Review
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501 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 2 institutions in 1 country.

Spencer C Wei1] Department of Pharmacology, University of California, San Diego, 9500 Gilman Drive La Jolla, California 92093-0819, USA [2] The Biomedical Sciences Graduate Program, University of California, San Diego, 9500 Gilman Drive La Jolla, California 92093-0819, USA.
Laurent FattetDepartment of Pharmacology, University of California, San Diego, 9500 Gilman Drive La Jolla, California 92093-0819, USA.
Jeff H TsaiDepartment of Pharmacology, University of California, San Diego, 9500 Gilman Drive La Jolla, California 92093-0819, USA.
Yurong GuoHoward Hughes Medical Institute, University of California, San Diego, 9500 Gilman Drive La Jolla, California 92093-0819, USA.
Vincent H Pai1] Department of Pharmacology, University of California, San Diego, 9500 Gilman Drive La Jolla, California 92093-0819, USA [2] The Biomedical Sciences Graduate Program, University of California, San Diego, 9500 Gilman Drive La Jolla, California 92093-0819, USA.
Hannah E Majeski1] Department of Pharmacology, University of California, San Diego, 9500 Gilman Drive La Jolla, California 92093-0819, USA [2] The Biomedical Sciences Graduate Program, University of California, San Diego, 9500 Gilman Drive La Jolla, California 92093-0819, USA.
Albert C ChenDepartment of Bioengineering, University of California, San Diego, 9500 Gilman Drive La Jolla, California 92093-0819, USA.
Robert L SahDepartment of Bioengineering, University of California, San Diego, 9500 Gilman Drive La Jolla, California 92093-0819, USA.
Susan S Taylor1] Department of Pharmacology, University of California, San Diego, 9500 Gilman Drive La Jolla, California 92093-0819, USA [2] Howard Hughes Medical Institute, University of California, San Diego, 9500 Gilman Drive La Jolla, California 92093-0819, USA [3] Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive La Jolla, California 92093-0819, USA.
Adam J EnglerDepartment of Bioengineering, University of California, San Diego, 9500 Gilman Drive La Jolla, California 92093-0819, USA.
Jing Yang1] Department of Pharmacology, University of California, San Diego, 9500 Gilman Drive La Jolla, California 92093-0819, USA [2] Department of Pediatrics, University of California, San Diego, 9500 Gilman Drive La Jolla, California 92093-0819, USA.
University of California, San Diego · USHoward Hughes Medical Institute · US

Funding

VIRAL MALIGNANCYP30CA023100 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DIANE M SIMEONE · 1985 to 2026
$124.9M
Project# 4: INTERACTIONS OF ANCHORING PROTEINS WITH THEIR TARGETSP01DK054441 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI TAYLOR, SUSAN S. · 1999 to 2017
$27.3M
TISSUE ACQUISITION, MORPHOLOGY, AND CELL CULTUREP01AG007996 · NIA · UNIVERSITY OF CALIFORNIA SAN DIEGO · PI LOTZ, MARTIN K · 1989 to 2016
$26.0M
GRADUATE TRAINING IN CELLULAR &MOLECULAR PHARMACOLOGYT32GM007752 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BROWN, JOAN HELLER, HANDEL, TRACY M · 1985 to 2023
$13.5M
U of Calif, San Diego Neuroscience Microscopy ImagingP30NS047101 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GLEESON, JOSEPH G, ZHENG, BINHAI · 2003 to 2022
$9.0M
Predoctoral and Postdoctoral Training in Cancer Cell BiologyT32CA067754 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI JEAN Y.J. WANG · 1995 to 2026
$6.5M
Epithelial-Mesenchymal Transition in Tumor MetastasisDP2OD002420 · OD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI YANG, JING · 2007 to 2007
$2.3M
Regulation of Tumor Invasion by Twist1R01CA168689 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI YANG, JING · 2012 to 2016
$1.7M
MOLECULAR PATHOLOGY OF CANCER TRAINING GRANTT32CA077109 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KAMPS, MARK P · 1998 to 2009
$1.2M
Howard Hughes Medical InstituteNCI NIH HHS 1R01CA168689NCI NIH HHS 2T32CA067754NCI NIH HHS 5T32CA077109NCI NIH HHS P30 CA023100NCI NIH HHS P30CA23100NCI NIH HHS R01 CA168689NCI NIH HHS T32 CA067754NCI NIH HHS T32 CA077109NIA NIH HHS P01 AG007996NIA NIH HHS P01AG007996NIDDK NIH HHS DK54441NIDDK NIH HHS P01 DK054441NIGMS NIH HHS T32 GM007752NIH HHS DP2 OD002420NIH HHS DP2OD002420-01NINDS NIH HHS P30 NS047101NINDS NIH HHS P30NS047101
6 · The paper itself

Abstract

Matrix stiffness potently regulates cellular behaviour in various biological contexts. In breast tumours, the presence of dense clusters of collagen fibrils indicates increased matrix stiffness and correlates with poor survival. It is unclear how mechanical inputs are transduced into transcriptional outputs to drive tumour progression. Here we report that TWIST1 is an essential mechanomediator that promotes epithelial-mesenchymal transition (EMT) in response to increasing matrix stiffness. High matrix stiffness promotes nuclear translocation of TWIST1 by releasing TWIST1 from its cytoplasmic binding partner G3BP2. Loss of G3BP2 leads to constitutive TWIST1 nuclear localization and synergizes with increasing matrix stiffness to induce EMT and promote tumour invasion and metastasis. In human breast tumours, collagen fibre alignment, a marker of increasing matrix stiffness, and reduced expression of G3BP2 together predict poor survival. Our findings reveal a TWIST1-G3BP2 mechanotransduction pathway that responds to biomechanical signals from the tumour microenvironment to drive EMT, invasion and metastasis.

Indexed as

Epithelial-Mesenchymal TransitionMechanotransduction, CellularActive Transport, Cell NucleusAdaptor Proteins, Signal TransducingAnimalsBreast NeoplasmsCarcinoma, Intraductal, NoninfiltratingCarrier ProteinsCell Line, TumorCell-Matrix JunctionsCollagenDatabases, GeneticDisease-Free SurvivalElasticityExtracellular MatrixFemaleAdaptor Proteins, Signal TransducingCarrier ProteinsCollagenG3BP2 protein, humanNuclear ProteinsRNA-Binding ProteinsTWIST1 protein, humanTwist-Related Protein 1

Identifiers

PMID25893917
PMCPMC4452027
OpenAlexW2024315189

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Registered trials

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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.