Evidence map›Paper›PMID 27820599›Full record

ArticleNature cell biology2016

Tissue mechanics promote IDH1-dependent HIF1α-tenascin C feedback to regulate glioblastoma aggression.

Yekaterina A Miroshnikova, Janna K Mouw, J Matthew Barnes, Michael W Pickup, Johnathan N Lakins, Youngmi Kim, Khadjia Lobo, Anders I Persson, Gerald F Reis, Tracy R McKnight and 3 more

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

Article in Nature cell biology, 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 223 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
223citing papers in PubMed, 2 pooled it
13.5field-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

223 citing papers in PubMed, 2 syntheses or guidelines pooled it, 379 citations in OpenAlex.

  1. Pooled it
  2. Physical Forces in Glioblastoma Migration: A Systematic Review.International journal of molecular sciences · 2022
    Pooled it
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  16. Microengineered Gradient Hydrogels for Mechanobiology.Advanced healthcare materials · 2026
    Review
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  18. Review
  19. Article
  20. Review

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 4 institutions in 1 country.

Yekaterina A MiroshnikovaCenter for Bioengineering and Tissue Regeneration, Department of Surgery, University of California San Francisco, San Francisco, California 94143, USA.
Janna K MouwCenter for Bioengineering and Tissue Regeneration, Department of Surgery, University of California San Francisco, San Francisco, California 94143, USA.
J Matthew BarnesCenter for Bioengineering and Tissue Regeneration, Department of Surgery, University of California San Francisco, San Francisco, California 94143, USA.
Michael W PickupCenter for Bioengineering and Tissue Regeneration, Department of Surgery, University of California San Francisco, San Francisco, California 94143, USA.
Johnathan N LakinsCenter for Bioengineering and Tissue Regeneration, Department of Surgery, University of California San Francisco, San Francisco, California 94143, USA.
Youngmi KimDivision of Human Biology and Solid Tumor Translational Research, Fred Hutchinson Cancer Research Center, Department of Neurosurgery and Alvord Brain Tumor Center, University of Washington, Seattle, Washington 98109, USA.
Khadjia LoboMagnetic Resonance Science Center, Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California 94143, USA.
Anders I PerssonDepartment of Neurology, University of California, San Francisco, California 94143, USA.
Gerald F ReisDepartment of Pathology, University of California, San Francisco, California 94143, USA.
Tracy R McKnightMagnetic Resonance Science Center, Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California 94143, USA.
Eric C HollandDivision of Human Biology and Solid Tumor Translational Research, Fred Hutchinson Cancer Research Center, Department of Neurosurgery and Alvord Brain Tumor Center, University of Washington, Seattle, Washington 98109, USA.
Joanna J PhillipsDepartment of Neurological Surgery, University of California San Francisco, San Francisco, California 94158, USA.
Valerie M WeaverCenter for Bioengineering and Tissue Regeneration, Department of Surgery, University of California San Francisco, San Francisco, California 94143, USA.
University of California, San Francisco · USUniversity of Washington · USBroad Center · USNeurological Surgery · US

Funding

Tissue CoreP50CA097257 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Joseph F Costello · 2002 to 2026
$57.4M
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
Project 3: Physical and Metabolic Constraints of Cancer Cell InvasionU54CA210184 · NCI · CORNELL UNIVERSITY · PI CERIONE, RICHARD A. · 2016 to 2020
$10.2M
The vascular niche in glioma propagation and resistance to therapyU54CA163155 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BERGERS, GABRIELE, WEAVER, VALERIE MARIE · 2011 to 2015
$4.4M
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
A biophysical stromal basis for radiation sensitivity in ductal carcinoma in situR01CA174929 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI PARK, CATHERINE C, WEAVER, VALERIE MARIE · 2014 to 2018
$3.1M
Tension-Stat3-miR-mediated metastasisR01CA192914 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SEEWALDT, VICTORIA L., WEAVER, VALERIE MARIE · 2015 to 2019
$2.9M
Extracellular Sulfatases As Novel Biomarkers For Early Detection of CancerU01CA168878 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LEMJABBAR-ALAOUI, HASSAN, PHILLIPS, JOANNA · 2012 to 2016
$2.2M
Collagen remodeling and tumor progressionR01CA138818 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI WEAVER, VALERIE MARIE · 2010 to 2014
$2.0M
Heparan sulfate proteoglycans as critical regulators of brain cancer malignancyR01NS081117 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI PHILLIPS, JOANNA · 2012 to 2016
$1.7M
Antisecretory factor as a novel therapeutic agent in human glioblastomaR21NS088114 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI PERSSON, PER ANDERS INGEMAR · 2014 to 2015
$395k
NCI NIH HHS F31 CA180422NCI NIH HHS P50 CA097257NCI NIH HHS R01 CA138818NCI NIH HHS R01 CA174929NCI NIH HHS R01 CA192914NCI NIH HHS T32 CA108462NCI NIH HHS U01 CA168878NCI NIH HHS U01 CA202241NCI NIH HHS U54 CA143836NCI NIH HHS U54 CA163155NCI NIH HHS U54 CA210184NINDS NIH HHS R01 NS081117NINDS NIH HHS R21 NS088114
6 · The paper itself

Abstract

Increased overall survival for patients with glioma brain tumours is associated with mutations in the metabolic regulator isocitrate dehydrogenase 1 (IDH1). Gliomas develop within a mechanically challenged microenvironment that is characterized by a dense extracellular matrix (ECM) that compromises vascular integrity to induce hypoxia and activate HIF1α. We found that glioma aggression and patient prognosis correlate with HIF1α levels and the stiffness of a tenascin C (TNC)-enriched ECM. Gain- and loss-of-function xenograft manipulations demonstrated that a mutant IDH1 restricts glioma aggression by reducing HIF1α-dependent TNC expression to decrease ECM stiffness and mechanosignalling. Recurrent IDH1-mutant patient gliomas had a stiffer TNC-enriched ECM that our studies attributed to reduced miR-203 suppression of HIF1α and TNC mediated via a tension-dependent positive feedback loop. Thus, our work suggests that elevated ECM stiffness can independently foster glioblastoma aggression and contribute to glioblastoma recurrence via bypassing the protective activity of IDH1 mutational status.

Indexed as

Feedback, PhysiologicalBrain NeoplasmsCell Line, TumorExtracellular MatrixFluorescent Antibody TechniqueGlioblastomaHumansHypoxia-Inducible Factor 1, alpha SubunitIsocitrate DehydrogenaseMechanotransduction, CellularMicroRNAsMutationNeoplasm InvasivenessSignal TransductionTenascinXenograft Model Antitumor AssaysHypoxia-Inducible Factor 1, alpha SubunitIDH1 protein, humanIsocitrate DehydrogenaseMicroRNAsMIRN203 microRNA, humanTenascin

Identifiers

PMID27820599
PMCPMC5361403
OpenAlexW2555999948

What OpenQuestion holds

Textmetadata
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.