Evidence map›Paper›PMID 22561374›Full record

ArticleNucleic acids research2012

Targeted silencing of the oncogenic transcription factor SOX2 in breast cancer.

Sabine Stolzenburg, Marianne G Rots, Adriana S Beltran, Ashley G Rivenbark, Xinni Yuan, Haili Qian, Brian D Strahl, Pilar Blancafort

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
95citing papers in PubMed, 1 pooled it
9.2field-weighted citation impact, top 1% 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

95 citing papers in PubMed, 1 synthesis or guideline pooled it, 169 citations in OpenAlex.

  1. Prognostic value of Sox2 expression in digestive tract cancers: A meta-analysis.Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban · 2016
    Pooled it
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35 more citing papers are in PubMed but not listed here.

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

8 authors at 3 institutions in 3 countries.

Sabine StolzenburgEpigenetic Editing, Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
Marianne G Rots
Adriana S Beltran
Ashley G Rivenbark
Xinni Yuan
Haili Qian
Brian D Strahl
Pilar Blancafort
University of North Carolina at Chapel Hill · USChinese Academy of Medical Sciences & Peking Union Medical College · CNUniversity Medical Center Groningen · NL

Funding

Re-activation of maspin tumor suppressor gene by designed transcription factorsR01CA125273 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI GRAVES, LEE M · 2007 to 2011
$1.9M
Targeted epigenetic silencing of oncogenic Transcription Factors (PQ18)R01CA170370 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BLANCAFORT, PILAR · 2012 to 2015
$900k
NCI NIH HHS 1R01CA125273NCI NIH HHS 3R01CA125273-03S1NCI NIH HHS R01 CA170370
6 · The paper itself

Abstract

The transcription factor (TF) SOX2 is essential for the maintenance of pluripotency and self-renewal in embryonic stem cells. In addition to its normal stem cell function, SOX2 over-expression is associated with cancer development. The ability to selectively target this and other oncogenic TFs in cells, however, remains a significant challenge due to the 'undruggable' characteristics of these molecules. Here, we employ a zinc finger (ZF)-based artificial TF (ATF) approach to selectively suppress SOX2 gene expression in cancer cells. We engineered four different proteins each composed of 6ZF arrays designed to bind 18 bp sites in the SOX2 promoter and enhancer region, which controls SOX2 methylation. The 6ZF domains were linked to the Kruppel Associated Box (SKD) repressor domain. Three engineered proteins were able to bind their endogenous target sites and effectively suppress SOX2 expression (up to 95% repression efficiencies) in breast cancer cells. Targeted down-regulation of SOX2 expression resulted in decreased tumor cell proliferation and colony formation in these cells. Furthermore, induced expression of an ATF in a mouse model inhibited breast cancer cell growth. Collectively, these findings demonstrate the effectiveness and therapeutic potential of engineered ATFs to mediate potent and long-lasting down-regulation of oncogenic TF expression in cancer cells.

Indexed as

Gene SilencingAnimalsBreast NeoplasmsCell Line, TumorCell ProliferationDNAFemaleHumansMiceProtein EngineeringSOXB1 Transcription FactorsTranscription FactorsXenograft Model Antitumor AssaysDNASOX2 protein, humanSOXB1 Transcription FactorsTranscription Factors

Identifiers

PMID22561374
PMCPMC3413152
OpenAlexW1991113366

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.