Evidence map›Paper›PMID 29754406›Full record

ArticleMolecular oncology2018

Targeting TWIST1 through loss of function inhibits tumorigenicity of human glioblastoma.

Andrei M Mikheev, Svetlana A Mikheeva, Liza J Severs, Cory C Funk, Lei Huang, José L McFaline-Figueroa, Jeanette Schwensen, Cole Trapnell, Nathan D Price, Stephen Wong and 1 more

Open access · goldAbstract read
In one paragraph

Article in Molecular oncology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
1.4field-weighted citation impact, top 21% 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

25 citing papers in PubMed, 33 citations in OpenAlex.

  1. Review
  2. Review
  3. Biomolecules & biomedicine · 2025
    Article
  4. Article
  5. Analysis of DNA Methylation in Gliomas: Assessment of Preanalytical Variables.Laboratory investigation; a journal of technical methods and pathology · 2024
    Article
  6. Loss of DNA Polymerase β Delays Atherosclerosis inInternational journal of molecular sciences · 2024
    Article
  7. Article
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  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. TCF21: a critical transcription factor in health and cancer.Journal of molecular medicine (Berlin, Germany) · 2020
    Review
  17. Article
  18. Article
  19. Article
  20. Article
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

11 authors at 6 institutions in 1 country.

Andrei M MikheevDepartment of Neurosurgery, Houston Methodist Hospital and Research Institute, Houston, TX, USA.
Svetlana A MikheevaDepartment of Neurosurgery, Houston Methodist Hospital and Research Institute, Houston, TX, USA.
Liza J SeversDepartment of Physiology and Biophysics, University of Washington, Seattle, WA, USA.
Cory C FunkInstitute for Systems Biology, Seattle, WA, USA.
Lei HuangDepartment of Systems Medicine& Bioengineering, Houston Methodist Hospital and Research Institute, Weil Cornell Medical College, Houston, TX, USA.
José L McFaline-FigueroaDepartment of Genome Sciences, University of Washington, Seattle, WA, USA.
Jeanette SchwensenDepartment of Neurosurgery and Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, USA.
Cole TrapnellDepartment of Genome Sciences, University of Washington, Seattle, WA, USA.
Nathan D PriceInstitute for Systems Biology, Seattle, WA, USA.
Stephen WongDepartment of Systems Medicine& Bioengineering, Houston Methodist Hospital and Research Institute, Weil Cornell Medical College, Houston, TX, USA.
Robert C RostomilyDepartment of Neurosurgery, Houston Methodist Hospital and Research Institute, Houston, TX, USA.
University of Washington · USCornell University · USHouston Methodist · USInstitute for Systems Biology · USCalifornia Institute for Regenerative Medicine · USMethodist Hospital · US

Funding

Tumor mutation signaturesP01CA077852 · NCI · UNIVERSITY OF WASHINGTON · PI SIDOROVA, JULIA · 1999 to 2019
$26.0M
CARDIOVASCULAR RESEARCH TRAINING PROGRAMT32HL007828 · NHLBI · UNIVERSITY OF WASHINGTON · PI Francis Kim, Farid Moussavi-Harami · 1997 to 2026
$10.2M
Intellectual and Developmental Disabilities Research CenterU54HD083091 · NICHD · UNIVERSITY OF WASHINGTON · PI DOHERTY, DANIEL · 2014 to 2019
$7.9M
Therapeutically relevant targets of Twist1 dimers in gliomaR01NS091251 · NINDS · UNIVERSITY OF WASHINGTON · PI ROSTOMILY, ROBERT C · 2015 to 2020
$1.8M
TWIST1 as a target for inhibition of glioma invasionR01CA136808 · NCI · UNIVERSITY OF WASHINGTON · PI ROSTOMILY, ROBERT C · 2011 to 2015
$1.7M
Generation of TWIST1 reporters through characterization of TWIST1 dependent netwoR21NS082542 · NINDS · UNIVERSITY OF WASHINGTON · PI MIKHEEV, ANDREI M · 2013 to 2014
$476k
NCI NIH HHS P01 CA077852NCI NIH HHS R01 CA136808NHLBI NIH HHS T32 HL007828NICHD NIH HHS U54 HD083091NINDS NIH HHS R01 NS091251NINDS NIH HHS R21 NS082542
6 · The paper itself

Abstract

TWIST1 (TW) is a bHLH transcription factor (TF) and master regulator of the epithelial-to-mesenchymal transition (EMT). In vitro, TW promotes mesenchymal change, invasion, and self-renewal in glioblastoma (GBM) cells. However, the potential therapeutic relevance of TW has not been established through loss-of-function studies in human GBM cell xenograft models. The effects of TW loss of function (gene editing and knockdown) on inhibition of tumorigenicity of U87MG and GBM4 glioma stem cells were tested in orthotopic xenograft models and conditional knockdown in established flank xenograft tumors. RNAseq and the analysis of tumors investigated putative TW-associated mechanisms. Multiple bioinformatic tools revealed significant alteration of ECM, membrane receptors, signaling transduction kinases, and cytoskeleton dynamics leading to identification of PI3K/AKT signaling. We experimentally show alteration of AKT activity and periostin (POSTN) expression in vivo and/or in vitro. For the first time, we show that effect of TW knockout inhibits AKT activity in U87MG cells in vivo independent of PTEN mutation. The clinical relevance of TW and candidate mechanisms was established by analysis of the TCGA and ENCODE databases. TW expression was associated with decreased patient survival and LASSO regression analysis identified POSTN as one of top targets of TW in human GBM. While we previously demonstrated the role of TW in promoting EMT and invasion of glioma cells, these studies provide direct experimental evidence supporting protumorigenic role of TW independent of invasion in vivo and the therapeutic relevance of targeting TW in human GBM. Further, the role of TW driving POSTN expression and AKT signaling suggests actionable targets, which could be leveraged to mitigate the oncogenic effects of TW in GBM.

Indexed as

Brain NeoplasmsCarcinogenesisCell Adhesion MoleculesCell Line, TumorGene EditingGene Expression Regulation, NeoplasticGene Knockdown TechniquesGlioblastomaHumansNeoplastic Stem CellsNuclear ProteinsPhosphorylationProto-Oncogene Proteins c-aktSurvival AnalysisTwist-Related Protein 1Cell Adhesion MoleculesNuclear ProteinsPOSTN protein, humanProto-Oncogene Proteins c-aktTWIST1 protein, humanTwist-Related Protein 1AKTglioblastomaglioma stem cellsperiostintumorigenicityTWIST1

Identifiers

PMID29754406
PMCPMC6026950
OpenAlexW2800037441

What OpenQuestion holds

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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.