Evidence map›Paper›PMID 35422476›Full record

ArticleOncogene2022

Inhibitor of DNA binding 2 (ID2) regulates the expression of developmental genes and tumorigenesis in ewing sarcoma.

Stacia L Koppenhafer, Kelli L Goss, Ellen Voigt, Emma Croushore, William W Terry, Jason Ostergaard, Peter M Gordon, David J Gordon

Open access · greenAbstract read
In one paragraph

Article in Oncogene, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.2field-weighted citation impact, top 21% 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

8 citing papers in PubMed, 8 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. ER chaperone GRP78/BiP translocates to the nucleus under stress and acts as a transcriptional regulator.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  8. 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

8 authors at 2 institutions in 1 country.

Stacia L KoppenhaferDepartment of Pediatrics, Division of Pediatric Hematology/Oncology, University of Iowa, Iowa City, IA, 52242, USA.
Kelli L GossDepartment of Pediatrics, Division of Pediatric Hematology/Oncology, University of Iowa, Iowa City, IA, 52242, USA.
Ellen VoigtCarver College of Medicine, University of Iowa, Iowa City, IA, 52242, USA.
Emma CroushoreDepartment of Pediatrics, Division of Pediatric Hematology/Oncology, University of Iowa, Iowa City, IA, 52242, USA.
William W TerryDepartment of Pediatrics, Division of Pediatric Hematology/Oncology, University of Iowa, Iowa City, IA, 52242, USA.
Jason OstergaardDepartment of Pediatrics, Division of Pediatric Hematology/Oncology, University of Minnesota, Minneapolis, MN, 55455, USA.
Peter M GordonDepartment of Pediatrics, Division of Pediatric Hematology/Oncology, University of Minnesota, Minneapolis, MN, 55455, USA.
David J GordonDepartment of Pediatrics, Division of Pediatric Hematology/Oncology, University of Iowa, Iowa City, IA, 52242, USA. david-j-gordon@uiowa.edu.ORCID http://orcid.org/0000-0003-1830-4371
University of Iowa · USUniversity of Minnesota · US

Funding

Viral VectorP30CA086862 · NCI · UNIVERSITY OF IOWA · PI Christopher K Laubenthal · 2000 to 2026
$70.0M
Medical Scientist Training ProgramT32GM139776 · NIGMS · UNIVERSITY OF IOWA · PI Gordon F Buchanan · 2021 to 2026
$6.4M
Gene Expression Signature Based Screening in Ewing SarcomaR37CA217910 · NCI · UNIVERSITY OF IOWA · PI GORDON, DAVID J · 2018 to 2024
$2.6M
Overcoming Leukemia Chemoresistance in the Central Nervous SystemR37CA240846 · NCI · UNIVERSITY OF MINNESOTA · PI PETER M GORDON · 2020 to 2026
$2.4M
NCI NIH HHS R37 CA217910NCI NIH HHS R37 CA240846NIGMS NIH HHS T32 GM139776
6 · The paper itself

Abstract

Sarcomas are difficult to treat and the therapy, even when effective, is associated with long-term and life-threatening side effects. In addition, the treatment regimens for many sarcomas, including Ewing sarcoma, rhabdomyosarcoma, and osteosarcoma, are relatively unchanged over the past two decades, indicating a critical lack of progress. Although differentiation-based therapies are used for the treatment of some cancers, the application of this approach to sarcomas has proven challenging. Here, using a CRISPR-mediated gene knockout approach, we show that Inhibitor of DNA Binding 2 (ID2) is a critical regulator of developmental-related genes and tumor growth in vitro and in vivo in Ewing sarcoma tumors. We also identified that homoharringtonine, which is an inhibitor of protein translation and FDA-approved for the treatment of leukemia, decreases the level of the ID2 protein and significantly reduces tumor growth and prolongs mouse survival in an Ewing sarcoma xenograft model. Furthermore, in addition to targeting ID2, homoharringtonine also reduces the protein levels of ID1 and ID3, which are additional members of the ID family of proteins with well-described roles in tumorigenesis, in multiple types of cancer. Overall, these results provide insight into developmental regulation in Ewing sarcoma tumors and identify a novel, therapeutic approach to target the ID family of proteins using an FDA-approved drug.

Indexed as

Inhibitor of Differentiation Protein 2Sarcoma, EwingAnimalsCarcinogenesisCell Transformation, NeoplasticGenes, DevelopmentalHomoharringtonineHumansMiceProteinsHomoharringtonineID2 protein, humanInhibitor of Differentiation Protein 2Proteins

Identifiers

PMID35422476
PMCPMC9107507
OpenAlexW4224049892

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.