Evidence map›Paper›PMID 31570734›Full record

ArticleScientific reports2019

Targeted genomic CRISPR-Cas9 screen identifies MAP4K4 as essential for glioblastoma invasion.

Laura M Prolo, Amy Li, Scott F Owen, Jonathon J Parker, Kara Foshay, Ryan T Nitta, David W Morgens, Sara Bolin, Christy M Wilson, Johana C M Vega L and 7 more

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

Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
4.1field-weighted citation impact, top 5% 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

38 citing papers in PubMed, 57 citations in OpenAlex.

  1. The Role of CRISPR and Its Therapeutic Applications in Glioblastoma.International journal of molecular sciences · 2026
    Review
  2. Review
  3. Review
  4. Review
  5. Review
  6. Review
  7. Review
  8. Review
  9. Article
  10. Unlocking Glioblastoma Vulnerabilities with CRISPR-Based Genetic Screening.International journal of molecular sciences · 2024
    Review
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Review
  19. Review
  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

17 authors at 3 institutions in 1 country.

Laura M ProloStanford University School of Medicine, Department of Neurosurgery, 300 Pasteur Dr, Stanford, CA, 94305, USA.
Amy LiStanford University School of Medicine, Department of Genetics, 291 Campus Dr, Stanford, CA, 94305, USA.
Scott F OwenJ. David Gladstone Institute of Neurological Disease, 1650 Owens St, San Francisco, CA, 94158, USA.
Jonathon J ParkerStanford University School of Medicine, Department of Neurosurgery, 300 Pasteur Dr, Stanford, CA, 94305, USA.
Kara FoshayInova Neuroscience and Spine Institute, Inova Health Systems, 8110 Gatehouse Rd, Falls Church, VA, 22042, USA.
Ryan T NittaStanford University School of Medicine, Department of Neurosurgery, 300 Pasteur Dr, Stanford, CA, 94305, USA.
David W MorgensStanford University School of Medicine, Department of Genetics, 291 Campus Dr, Stanford, CA, 94305, USA.
Sara BolinStanford University School of Medicine, Department of Neurosurgery, 300 Pasteur Dr, Stanford, CA, 94305, USA.ORCID http://orcid.org/0000-0003-2835-1518
Christy M WilsonStanford University School of Medicine, Department of Neurosurgery, 300 Pasteur Dr, Stanford, CA, 94305, USA.
Johana C M Vega LStanford University School of Medicine, Department of Neurosurgery, 300 Pasteur Dr, Stanford, CA, 94305, USA.
Emily J LuoStanford University School of Medicine, Department of Neurosurgery, 300 Pasteur Dr, Stanford, CA, 94305, USA.
Gigi NwagboStanford University School of Medicine, Department of Neurosurgery, 300 Pasteur Dr, Stanford, CA, 94305, USA.
Allen WaziriInova Neuroscience and Spine Institute, Inova Health Systems, 8110 Gatehouse Rd, Falls Church, VA, 22042, USA.
Gordon LiStanford University School of Medicine, Department of Neurosurgery, 300 Pasteur Dr, Stanford, CA, 94305, USA.
Richard J ReimerStanford University School of Medicine, Department of Neurology, 300 Pasteur Dr, Stanford, CA, 94305, USA.
Michael C BassikStanford University School of Medicine, Department of Genetics, 291 Campus Dr, Stanford, CA, 94305, USA.
Gerald A GrantStanford University School of Medicine, Department of Neurosurgery, 300 Pasteur Dr, Stanford, CA, 94305, USA. ggrant2@stanford.edu.
Stanford University · USInova Health System · USGladstone Institutes · US

Funding

Translational Oncology Research Program (Project-005)P30CA124435 · NCI · STANFORD UNIVERSITY · PI Melinda L. Telli · 2007 to 2026
$71.4M
Stanford Center for Clinical & Translational Education and Research (Spectrum)UL1TR003142 · NCATS · STANFORD UNIVERSITY · PI O'HARA, RUTH M · 2019 to 2023
$45.0M
Spectrum Stanford Center for clinical and Translational Research and EducationUL1TR001085 · NCATS · STANFORD UNIVERSITY · PI CULLEN, MARK RICHARD, GREENBERG, HARRY BERNARD · 2013 to 2017
$37.1M
Stanford Neurosurgery Resident Research Education ProgramR25NS065741 · NINDS · STANFORD UNIVERSITY · PI HAYDEN GEPHART, MELANIE, STEINBERG, GARY K · 2009 to 2022
$2.0M
NCATS NIH HHS UL1 TR001085NCATS NIH HHS UL1 TR003142NCI NIH HHS P30 CA124435NINDS NIH HHS R25 NS065741U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS) 5K08NA075144-05
6 · The paper itself

Abstract

Among high-grade brain tumors, glioblastoma is particularly difficult to treat, in part due to its highly infiltrative nature which contributes to the malignant phenotype and high mortality in patients. In order to better understand the signaling pathways underlying glioblastoma invasion, we performed the first large-scale CRISPR-Cas9 loss of function screen specifically designed to identify genes that facilitate cell invasion. We tested 4,574 genes predicted to be involved in trafficking and motility. Using a transwell invasion assay, we discovered 33 genes essential for invasion. Of the 11 genes we selected for secondary testing using a wound healing assay, 6 demonstrated a significant decrease in migration. The strongest regulator of invasion was mitogen-activated protein kinase 4 (MAP4K4). Targeting of MAP4K4 with single guide RNAs or a MAP4K4 inhibitor reduced migration and invasion in vitro. This effect was consistent across three additional patient derived glioblastoma cell lines. Analysis of epithelial-mesenchymal transition markers in U138 cells with lack or inhibition of MAP4K4 demonstrated protein expression consistent with a non-invasive state. Importantly, MAP4K4 inhibition limited migration in a subset of human glioma organotypic slice cultures. Our results identify MAP4K4 as a novel potential therapeutic target to limit glioblastoma invasion.

Indexed as

CRISPR-Associated Protein 9CRISPR-Cas SystemsBrain NeoplasmsGlioblastomaHumansIntracellular Signaling Peptides and ProteinsNeoplasm InvasivenessProtein Serine-Threonine KinasesCRISPR-Associated Protein 9Intracellular Signaling Peptides and ProteinsMAP4K4 protein, humanProtein Serine-Threonine Kinases

Identifiers

PMID31570734
PMCPMC6768851
OpenAlexW2975786428

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.