Evidence map›Paper›PMID 27089513›Full record

ArticleNature medicine2016

Genotype tunes pancreatic ductal adenocarcinoma tissue tension to induce matricellular fibrosis and tumor progression.

Hanane Laklai, Yekaterina A Miroshnikova, Michael W Pickup, Eric A Collisson, Grace E Kim, Alex S Barrett, Ryan C Hill, Johnathon N Lakins, David D Schlaepfer, Janna K Mouw and 12 more

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

Article in Nature medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 396 papers.

0numbers the graph read from it
0cells of the map it votes in
396citing papers in PubMed
27.9field-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

396 citing papers in PubMed, 587 citations in OpenAlex.

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  2. Spatial Configuration of Pancreatic Cancer Is Associated with Disease Recurrence after Neoadjuvant Therapy and Curative-Intent Resection.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
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  7. Beyond DNA damage: 3D tumor models and the integrin mechanobiology of radioresistance.Journal of experimental & clinical cancer research : CR · 2026
    Review
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  14. Glutamine-dependent changes in fibroblast-derived extracellular matrix dictate cancer cell behavior.Matrix biology : journal of the International Society for Matrix Biology · 2026
    Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. Review
  20. Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

22 authors at 9 institutions in 3 countries.

Hanane LaklaiCenter for Bioengineering and Tissue Regeneration, Department of Surgery, University of California, San Francisco, San Francisco, California, USA.
Yekaterina A MiroshnikovaCenter for Bioengineering and Tissue Regeneration, Department of Surgery, University of California, San Francisco, San Francisco, California, USA.
Michael W PickupCenter for Bioengineering and Tissue Regeneration, Department of Surgery, University of California, San Francisco, San Francisco, California, USA.
Eric A CollissonDepartment of Medicine, University of California, San Francisco, San Francisco, California, USA.
Grace E KimDepartment of Pathology, University of California, San Francisco, San Francisco, California, USA.
Alex S BarrettDepartment of Biochemistry and Molecular Genetics, University of Colorado, Denver, Aurora, Colorado, USA.
Ryan C HillDepartment of Biochemistry and Molecular Genetics, University of Colorado, Denver, Aurora, Colorado, USA.
Johnathon N LakinsCenter for Bioengineering and Tissue Regeneration, Department of Surgery, University of California, San Francisco, San Francisco, California, USA.
David D SchlaepferDepartment of Reproductive Medicine, University of California, San Diego Moores Cancer Center, La Jolla, California, USA.
Janna K MouwCenter for Bioengineering and Tissue Regeneration, Department of Surgery, University of California, San Francisco, San Francisco, California, USA.
Valerie S LeBleuDepartment of Cancer Biology, Metastasis Research Center, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
Nilotpal RoyDiabetes Center, Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
Sergey V NovitskiyDepartment of Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Julia S JohansenDepartment of Oncology, Herlev Hospital, Copenhagen University Hospital, Copenhagen, Denmark.
Valeria PoliDepartment of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Turin, Turin, Italy.ORCID 0000-0002-3739-3966
Raghu KalluriDepartment of Cancer Biology, Metastasis Research Center, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
Christine A Iacobuzio-DonahueDepartment of Pathology, David Rubenstein Center for Pancreatic Cancer Research, Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA.ORCID 0000-0002-4672-3023
Laura D WoodGastrointestinal and Liver Pathology Department, Johns Hopkins University, Baltimore, Maryland, USA.
Matthias HebrokDiabetes Center, Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
Kirk HansenDepartment of Biochemistry and Molecular Genetics, University of Colorado, Denver, Aurora, Colorado, USA.
Harold L MosesDepartment of Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Valerie M WeaverCenter for Bioengineering and Tissue Regeneration, Department of Surgery, University of California, San Francisco, San Francisco, California, USA.
University of California, San Francisco · USUniversity of Colorado Denver · USThe University of Texas MD Anderson Cancer Center · USVanderbilt University · USHerlev Hospital · DKJohns Hopkins University · USMemorial Sloan Kettering Cancer Center · USUniversity of California San Diego · USUniversity of Turin · IT

Funding

Colorado Clinical and Translational Sciences InstituteUL1TR001082 · NCATS · UNIVERSITY OF COLORADO DENVER · PI SOKOL, RONALD J. · 2013 to 2017
$48.0M
TRANS-NETWORK PROJECTSU54CA143836 · NCI · UNIVERSITY OF CALIFORNIA BERKELEY · PI LIPHARDT, JAN T. · 2009 to 2014
$15.1M
Molecular and Cellular Mechanisms in CancerT32CA108462 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GOGA, ANDREI · 2004 to 2024
$10.4M
Role of Focal Adhesion Kinase In TumorigenesisR01CA102310 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SCHLAEPFER, DAVID D · 2003 to 2019
$5.0M
ECM geometrical and mechanical properties modulate RTK signalingU01CA202241 · NCI · UNIVERSITY OF CALIFORNIA BERKELEY · PI GROVES, JAY T., WEAVER, VALERIE MARIE · 2015 to 2019
$3.3M
Role of Fibroblasts, Myeloid Cells and Matrix in PDACU01CA151925 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI KALLURI, RAGHU, MOSES, HAROLD L · 2010 to 2014
$3.2M
Tension-Stat3-miR-mediated metastasisR01CA192914 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SEEWALDT, VICTORIA L., WEAVER, VALERIE MARIE · 2015 to 2019
$2.9M
Collagen remodeling and tumor progressionR01CA138818 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI WEAVER, VALERIE MARIE · 2010 to 2014
$2.0M
Signaling Connections Controlling Cell Motility and InvasionR01CA180769 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SCHLAEPFER, DAVID D · 2013 to 2017
$1.9M
Epigenetic regulation of pancreatic cancerR01CA172045 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI HEBROK, MATTHIAS · 2014 to 2018
$1.6M
Crucial Microenvironmental Cofactors for Pancreatic Cancer PathogenesisR01CA178015 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI COLLISSON, ERIC · 2014 to 2018
$1.5M
Colorado Clinical and Translational Sciences InstituteTL1TR001081 · NCATS · UNIVERSITY OF COLORADO DENVER · PI SOKOL, RONALD J. · 2013 to 2017
$1.3M
NCATS NIH HHS TL1 TR001081NCATS NIH HHS UL1 TR001082NCI NIH HHS F31 CA180422NCI NIH HHS R01 CA102310NCI NIH HHS R01 CA138818NCI NIH HHS R01 CA172045NCI NIH HHS R01 CA178015NCI NIH HHS R01 CA180769NCI NIH HHS R01 CA192914NCI NIH HHS R33 CA183685NCI NIH HHS T32 CA108462NCI NIH HHS U01 CA151925NCI NIH HHS U01 CA202241NCI NIH HHS U54 CA143836
6 · The paper itself

Abstract

Fibrosis compromises pancreatic ductal carcinoma (PDAC) treatment and contributes to patient mortality, yet antistromal therapies are controversial. We found that human PDACs with impaired epithelial transforming growth factor-β (TGF-β) signaling have high epithelial STAT3 activity and develop stiff, matricellular-enriched fibrosis associated with high epithelial tension and shorter patient survival. In several KRAS-driven mouse models, both the loss of TGF-β signaling and elevated β1-integrin mechanosignaling engaged a positive feedback loop whereby STAT3 signaling promotes tumor progression by increasing matricellular fibrosis and tissue tension. In contrast, epithelial STAT3 ablation attenuated tumor progression by reducing the stromal stiffening and epithelial contractility induced by loss of TGF-β signaling. In PDAC patient biopsies, higher matricellular protein and activated STAT3 were associated with SMAD4 mutation and shorter survival. The findings implicate epithelial tension and matricellular fibrosis in the aggressiveness of SMAD4 mutant pancreatic tumors and highlight STAT3 and mechanics as key drivers of this phenotype.

Indexed as

AnimalsCarcinoma, Pancreatic DuctalChromatography, LiquidCollagenDisease Models, AnimalDisease ProgressionExtracellular MatrixFibrosisGenotypeHumansIntegrin beta ChainsMiceMicroscopy, Atomic ForceMutationPancreatic NeoplasmsPrognosisCollagenHras protein, mouseIntegrin beta ChainsProto-Oncogene Proteins p21(ras)Smad4 ProteinSMAD4 protein, humanSTAT3 protein, humanStat3 protein, mouseSTAT3 Transcription FactorTransforming Growth Factor beta

Identifiers

PMID27089513
PMCPMC4860133
OpenAlexW2337683177

What OpenQuestion holds

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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.