Evidence map›Paper›PMID 24518591›Full record

ArticleBritish journal of cancer2014

Guanine nucleotide exchange factor Dock7 mediates HGF-induced glioblastoma cell invasion via Rac activation.

D W Murray, S Didier, A Chan, V Paulino, L Van Aelst, R Ruggieri, N L Tran, A T Byrne, M Symons

Open access · hybridAbstract read
In one paragraph

Article in British journal of cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
1.1field-weighted citation impact, top 23% 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

30 citing papers in PubMed, 39 citations in OpenAlex.

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  16. Tumor Cell Invasion in Glioblastoma.International journal of molecular sciences · 2020
    Review
  17. The Role of Rho GTPases in Motility and Invasion of Glioblastoma Cells.Analytical cellular pathology (Amsterdam) · 2020
    Review
  18. Article
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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

9 authors at 5 institutions in 2 countries.

D W Murray1] Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, 123 St. Stephens' Green, Dublin 2, Ireland [2] Center for Oncology and Cell Biology, The Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, 350 Community Drive, Manhasset, NY 11030, USA.
S DidierCenter for Oncology and Cell Biology, The Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, 350 Community Drive, Manhasset, NY 11030, USA.
A ChanCenter for Oncology and Cell Biology, The Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, 350 Community Drive, Manhasset, NY 11030, USA.
V PaulinoCancer and Cell Biology Division, Translational Genomics Research Institute, 445 N. Fifth Street, Phoenix, AZ 85004, USA.
L Van AelstCold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.
R RuggieriCenter for Oncology and Cell Biology, The Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, 350 Community Drive, Manhasset, NY 11030, USA.
N L TranCancer and Cell Biology Division, Translational Genomics Research Institute, 445 N. Fifth Street, Phoenix, AZ 85004, USA.
A T Byrne1] Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, 123 St. Stephens' Green, Dublin 2, Ireland [2] UCD School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, Dublin 4, Ireland.
M SymonsCenter for Oncology and Cell Biology, The Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, 350 Community Drive, Manhasset, NY 11030, USA.
Feinstein Institute for Medical Research · USTranslational Genomics Research Institute · USCold Spring Harbor Laboratory · USRoyal College of Surgeons in Ireland · IEUniversity College Dublin · IE

Funding

Single-Cell Biology Shared ResourceP30CA045508 · NCI · COLD SPRING HARBOR LABORATORY · PI John Edward Moses · 1987 to 2026
$118.9M
Targeted MV-CEA as a Potent Antitumor Agent against GBMP50CA108961 · NCI · MAYO CLINIC ROCHESTER · PI O'NEILL, BRIAN PATRICK · 2004 to 2015
$22.5M
DOCK7 Signaling in Neuronal DevelopmentR01MH082808 · NIMH · COLD SPRING HARBOR LABORATORY · PI VAN AELST, LINDA · 2008 to 2017
$4.7M
Targeting the Fn14-Rac1 signaling pathway in invasive gliomasR01CA130940 · NCI · TRANSLATIONAL GENOMICS RESEARCH INST · PI TRAN, NHAN L · 2008 to 2012
$1.5M
Identification of RhoGEFs as novel therapeutic targets for malignant gliomaR21NS060023 · NINDS · FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH · PI SYMONS, MARC H · 2007 to 2008
$400k
NCI NIH HHS P30 CA045508NCI NIH HHS P50 CA108961NCI NIH HHS R01 CA130940NIMH NIH HHS R01 MH082808NINDS NIH HHS R21 NS060023
6 · The paper itself

Abstract

backgroundGlioblastoma multiforme (GBM), a highly invasive primary brain tumour, remains an incurable disease. Rho GTPases and their activators, guanine nucleotide exchange factors (GEFs), have central roles in GBM invasion. Anti-angiogenic therapies may stimulate GBM invasion via HGF/c-Met signalling. We aim to identify mediators of HGF-induced GBM invasion that may represent targets in a combination anti-angiogenic/anti-invasion therapeutic paradigm.

methodsGuanine nucleotide exchange factor expression was measured by microarray analysis and western blotting. Specific depletion of proteins was accomplished using siRNA. Cell invasion was determined using matrigel and brain slice assays. Cell proliferation and survival were monitored using sulforhodamine B and colony formation assays. Guanine nucleotide exchange factor and GTPase activities were determined using specific affinity precipitation assays.

resultsWe found that expression of Dock7, a GEF, is elevated in human GBM tissue in comparison with non-neoplastic brain. We showed that Dock7 mediates serum- and HGF-induced glioblastoma cell invasion. We also showed that Dock7 co-immunoprecipitates with c-Met and that this interaction is enhanced upon HGF stimulation in a manner that is dependent on the adaptor protein Gab1. Dock7 and Gab1 also co-immunoprecipitate in an HGF-dependent manner. Furthermore, Gab1 is required for HGF-induced Dock7 and Rac1 activation and glioblastoma cell invasion.

conclusionsDock7 mediates HGF-induced GBM invasion. Targeting Dock7 in GBM may inhibit c-MET-mediated invasion in tumours treated with anti-angiogenic regimens.

Indexed as

Adaptor Proteins, Signal TransducingAngiogenesis InhibitorsBrain NeoplasmsCell Growth ProcessesCell Line, TumorCell MovementCell SurvivalGlioblastomaGTPase-Activating ProteinsGuanine Nucleotide Exchange FactorsHepatocyte Growth FactorHumansProto-Oncogene Proteins c-metrac1 GTP-Binding Proteinrho GTP-Binding ProteinsAdaptor Proteins, Signal TransducingAngiogenesis InhibitorsDOCK7 protein, humanGAB1 protein, humanGTPase-Activating ProteinsGuanine Nucleotide Exchange FactorsHepatocyte Growth FactorHGF protein, humanMET protein, humanProto-Oncogene Proteins c-metrac1 GTP-Binding ProteinRAC1 protein, humanrho GTP-Binding Proteins

Identifiers

PMID24518591
PMCPMC3950876
OpenAlexW2018240980

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.