Evidence map›Paper›PMID 33989707›Full record

ArticleCancer letters2021

Cytomegalovirus infection of glioblastoma cells leads to NF-κB dependent upregulation of the c-MET oncogenic tyrosine kinase.

Harald Krenzlin, Mykola Zdioruk, Michal O Nowicki, Tomer Finkelberg, Naureen Keric, Niels Lemmermann, Magdalena Skubal, E Antonio Chiocca, Charles H Cook, Sean E Lawler

Open access · greenAbstract read
In one paragraph

Article in Cancer letters, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed, 1 pooled it
0.6field-weighted citation impact, top 32% 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

12 citing papers in PubMed, 1 synthesis or guideline pooled it, 12 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Does human cytomegalovirus provide a novel therapeutic target for patients with glioblastoma?Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025
    Review
  5. Environmental Hazards and Glial Brain Tumors: Association or Causation?International journal of molecular sciences · 2025
    Review
  6. Article
  7. Review
  8. Review
  9. Review
  10. Review
  11. Article
  12. Review
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

10 authors at 3 institutions in 2 countries.

Harald KrenzlinHarvey Cushing Neurooncology Laboratories, Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Department of Neurosurgery, University Hospital Mainz, Gutenberg University, Mainz, Germany.
Mykola ZdiorukHarvey Cushing Neurooncology Laboratories, Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Michal O NowickiHarvey Cushing Neurooncology Laboratories, Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Tomer FinkelbergHarvey Cushing Neurooncology Laboratories, Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Naureen KericDepartment of Neurosurgery, University Hospital Mainz, Gutenberg University, Mainz, Germany.
Niels LemmermannInstitute of Virology, University Hospital Mainz, Gutenberg University, Mainz, Germany.
Magdalena SkubalHarvey Cushing Neurooncology Laboratories, Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
E Antonio ChioccaHarvey Cushing Neurooncology Laboratories, Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Charles H CookDepartment of Surgery, Beth Israel Deaconess Medical Centre, Harvard Medical School, Boston, MA, USA. Electronic address: chcook@bidmc.harvard.edu.
Sean E LawlerHarvey Cushing Neurooncology Laboratories, Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: slawler@bwh.harvard.edu.
Brigham and Women's Hospital · USJohannes Gutenberg University Mainz · DEBeth Israel Deaconess Medical Center · US

Funding

The role of microvesicles in giloma virotherapyP01CA069246 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI CHAREST, ALAIN · 1996 to 2021
$30.9M
The Tumor Microenvironmental Barrier to Effective Viral OncolysisP01CA163205 · NCI · OHIO STATE UNIVERSITY · PI MICHAEL A CALIGIURI · 2013 to 2026
$26.0M
Investigating the cytomegalovirus link to glioblastoma using a novel mouse modelR01CA195532 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI CHIOCCA, E. ANTONIO · 2015 to 2019
$1.9M
Innovative approaches for the advancement of glioblastoma therapiesR50CA243706 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI NOWICKI, MICHAL OSKAR · 2019 to 2023
$662k
NCI NIH HHS P01 CA069246NCI NIH HHS P01 CA163205NCI NIH HHS R01 CA195532NCI NIH HHS R50 CA243706
6 · The paper itself

Abstract

Cytomegalovirus (CMV) is widespread in humans and has been implicated in glioblastoma (GBM) and other tumors. However, the role of CMV in GBM remains poorly understood and the mechanisms involved are not well-defined. The goal of this study was to identify candidate pathways relevant to GBM that may be modulated by CMV. Analysis of RNAseq data after CMV infection of patient-derived GBM cells showed significant upregulation of GBM-associated transcripts including the MET oncogene, which is known to play a role in a subset of GBM patients. These findings were validated in vitro in both mouse and human GBM cells. Using immunostaining and RT-PCR in vivo, we confirmed c-MET upregulation in a mouse model of CMV-driven GBM progression and in human GBM. siRNA knockdown showed that MET upregulation was dependent on CMV-induced upregulation of NF-κB signaling. Finally, proneural GBM xenografts overexpressing c-MET grew much faster in vivo than controls, suggesting a mechanism by which CMV infection of tumor cells could induce a more aggressive mesenchymal phenotype. These studies implicate the CMV-induced upregulation of c-MET as a potential mechanism involved in the effects of CMV on GBM growth.

Indexed as

AnimalsBrain NeoplasmsCytomegalovirus InfectionsGlioblastomaHumansMiceNF-kappa BProto-Oncogene Proteins c-metUp-RegulationNF-kappa BProto-Oncogene Proteins c-metc-METCytomegalovirusGlioblastomaNF-κB

Identifiers

PMID33989707
PMCPMC8209659
OpenAlexW3161400225

What OpenQuestion holds

Textmetadata
LicenceTDM
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.