Evidence map›Paper›PMID 28122245›Full record

ArticleCell reports2017

Oncogenes Activate an Autonomous Transcriptional Regulatory Circuit That Drives Glioblastoma.

Dinesh K Singh, Rahul K Kollipara, Vamsidara Vemireddy, Xiao-Li Yang, Yuxiao Sun, Nanda Regmi, Stefan Klingler, Kimmo J Hatanpaa, Jack Raisanen, Steve K Cho and 12 more

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

Article in Cell reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.

0numbers the graph read from it
0cells of the map it votes in
58citing papers in PubMed
7.5field-weighted citation impact, top 2% 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

58 citing papers in PubMed, 91 citations in OpenAlex.

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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

22 authors at 6 institutions in 1 country.

Dinesh K SinghDepartment of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Annette G. Strauss Center for Neuro-Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Eugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Rahul K KolliparaEugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Vamsidara VemireddyDepartment of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Annette G. Strauss Center for Neuro-Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Xiao-Li YangDepartment of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Annette G. Strauss Center for Neuro-Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Yuxiao SunDepartment of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Annette G. Strauss Center for Neuro-Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Nanda RegmiDepartment of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Annette G. Strauss Center for Neuro-Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Stefan KlinglerCold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Kimmo J HatanpaaAnnette G. Strauss Center for Neuro-Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Jack RaisanenAnnette G. Strauss Center for Neuro-Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Steve K ChoDepartment of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Annette G. Strauss Center for Neuro-Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Shyam SirasanagandlaAnnette G. Strauss Center for Neuro-Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Suraj NannepagaDepartment of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Annette G. Strauss Center for Neuro-Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Sara PiccirilloDepartment of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Tomoyuki MashimoAnnette G. Strauss Center for Neuro-Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Shan WangEugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Caroline G HumphriesEugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Bruce MickeyAnnette G. Strauss Center for Neuro-Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Neurological Surgery, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Elizabeth A MaherDepartment of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Annette G. Strauss Center for Neuro-Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Hongwu ZhengCold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Ryung S KimAlbert Einstein Cancer Center, Albert Einstein College of Medicine, New York, NY 10461, USA.
Ralf KittlerEugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: ralf.kittler@utsouthwestern.edu.
Robert M BachooDepartment of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Annette G. Strauss Center for Neuro-Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: robert.bachoo@utsouthwestern.edu.
The University of Texas Southwestern Medical Center · USCenter for Neuro-Oncology · USSouthwestern Medical Center · USCold Spring Harbor Laboratory · USAlbert Einstein College of Medicine · USNeurological Surgery · US

Funding

Single-Cell Biology Shared ResourceP30CA045508 · NCI · COLD SPRING HARBOR LABORATORY · PI John Edward Moses · 1987 to 2026
$118.9M
UT Southwestern Medical Center Simmons Comprehensive Cancer CenterP30CA142543 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI Sandi Leigh Pruitt · 2010 to 2026
$53.7M
Genetic Dissection of Glioblastoma: Cell of OriginR01NS065195 · NINDS · UT SOUTHWESTERN MEDICAL CENTER · PI BACHOO, ROBERT M. · 2010 to 2014
$1.7M
NCI NIH HHS P30 CA045508NCI NIH HHS P30 CA142543NINDS NIH HHS R01 NS065195
6 · The paper itself

Abstract

Efforts to identify and target glioblastoma (GBM) drivers have primarily focused on receptor tyrosine kinases (RTKs). Clinical benefits, however, have been elusive. Here, we identify an SRY-related box 2 (SOX2) transcriptional regulatory network that is independent of upstream RTKs and capable of driving glioma-initiating cells. We identified oligodendrocyte lineage transcription factor 2 (OLIG2) and zinc-finger E-box binding homeobox 1 (ZEB1), which are frequently co-expressed irrespective of driver mutations, as potential SOX2 targets. In murine glioma models, we show that different combinations of tumor suppressor and oncogene mutations can activate Sox2, Olig2, and Zeb1 expression. We demonstrate that ectopic co-expression of the three transcription factors can transform tumor-suppressor-deficient astrocytes into glioma-initiating cells in the absence of an upstream RTK oncogene. Finally, we demonstrate that the transcriptional inhibitor mithramycin downregulates SOX2 and its target genes, resulting in markedly reduced proliferation of GBM cells in vivo.

Indexed as

AnimalsAstrocytesBrainBrain NeoplasmsCell ProliferationCells, CulturedDisease Models, AnimalDown-RegulationErbB ReceptorsGefitinibGlioblastomaHumansMiceMice, Inbred NODMice, SCIDNeoplasm GradingErbB ReceptorsGefitinibOligodendrocyte Transcription Factor 2PlicamycinQuinazolinesReceptor, Platelet-Derived Growth Factor alphaSOXB1 Transcription FactorsZinc Finger E-box-Binding Homeobox 1astrocytebraincancerglioblastomaoncogenestem cellstargeted therapytranscription factor

Identifiers

PMID28122245
PMCPMC5321610
OpenAlexW2580293709

What OpenQuestion holds

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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.