Evidence map›Paper›PMID 31329165›Full record

ArticleThe Journal of clinical investigation2019

CIC-DUX4 oncoprotein drives sarcoma metastasis and tumorigenesis via distinct regulatory programs.

Ross A Okimoto, Wei Wu, Shigeki Nanjo, Victor Olivas, Yone K Lin, Rovingaile Kriska Ponce, Rieko Oyama, Tadashi Kondo, Trever G Bivona

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
3.7field-weighted citation impact, top 6% 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

42 citing papers in PubMed, 72 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Review
  9. Article
  10. ThebioRxiv : the preprint server for biology · 2024
    Article
  11. Review
  12. Article
  13. Review
  14. Article
  15. Molecular and therapeutic advancements in Capicua (Frontiers in cell and developmental biology · 2024
    Review
  16. Article
  17. Article
  18. Combined CDK4/6 and ERK1/2 Inhibition Enhances Antitumor Activity in NF1-Associated Plexiform Neurofibroma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023
    Article
  19. TheeLife · 2022
    Article
  20. 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

9 authors at 1 institution in 1 country.

Ross A OkimotoDepartment of Medicine.
Wei WuDepartment of Medicine.
Shigeki NanjoDepartment of Medicine.
Victor OlivasDepartment of Medicine.
Yone K LinDepartment of Medicine.
Rovingaile Kriska PonceDepartment of Medicine.
Rieko OyamaDivision of Rare Cancer Research, National Cancer Center Research Institute, Tokyo, Japan.
Tadashi KondoDivision of Rare Cancer Research, National Cancer Center Research Institute, Tokyo, Japan.
Trever G BivonaDepartment of Medicine.
UCSF Helen Diller Family Comprehensive Cancer Center · US

Funding

UCSF Project 1U54CA224081 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Trever G Bivona, Jack Roth · 2017 to 2026
$12.9M
The Cancer Target Discovery and Development Network at UCSFU01CA217882 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BANDYOPADHYAY, SOURAV, BIVONA, TREVER G · 2017 to 2021
$5.2M
Characterization of YAP as a rational companion target in lung cancerR01CA204302 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Trever G Bivona · 2017 to 2026
$3.7M
Rational Combined Inhibition of NF-kB and EGFR to Optimize Lung Cancer TreatmentR01CA169338 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BIVONA, TREVER G · 2013 to 2023
$3.4M
Optimizing biologically-based rational polytherapy in ALK+ lung cancerR01CA211052 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BIVONA, TREVER G · 2017 to 2021
$1.8M
Therapeutic rescue of the transcriptional repressor Capicua to inhibit lung cancer metastasisK08CA222625 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI OKIMOTO, ROSS · 2018 to 2022
$887k
NCI NIH HHS K08 CA222625NCI NIH HHS R01 CA169338NCI NIH HHS R01 CA204302NCI NIH HHS R01 CA211052NCI NIH HHS U01 CA217882NCI NIH HHS U54 CA224081
6 · The paper itself

Abstract

Transcription factor fusion genes create oncoproteins that drive oncogenesis and represent challenging therapeutic targets. Understanding the molecular targets by which such fusion oncoproteins promote malignancy offers an approach to develop rational treatment strategies to improve clinical outcomes. Capicua-double homeobox 4 (CIC-DUX4) is a transcription factor fusion oncoprotein that defines certain undifferentiated round cell sarcomas with high metastatic propensity and poor clinical outcomes. The molecular targets regulated by the CIC-DUX4 oncoprotein that promote this aggressive malignancy remain largely unknown. We demonstrated that increased expression of ETS variant 4 (ETV4) and cyclin E1 (CCNE1) occurs via neomorphic, direct effects of CIC-DUX4 and drives tumor metastasis and survival, respectively. We uncovered a molecular dependence on the CCNE-CDK2 cell cycle complex that renders CIC-DUX4-expressing tumors sensitive to inhibition of the CCNE-CDK2 complex, suggesting a therapeutic strategy for CIC-DUX4-expressing tumors. Our findings highlight a paradigm of functional diversification of transcriptional repertoires controlled by a genetically aberrant transcriptional regulator, with therapeutic implications.

Indexed as

AnimalsCarcinogenesisCell Line, TumorCyclin-Dependent Kinase 2Cyclin EFemaleHumansMiceMice, SCIDNeoplasm MetastasisNeoplasms, ExperimentalOncogene ProteinsOncogene Proteins, FusionProto-Oncogene Proteins c-etsSarcomaTranscription, GeneticCCNE1 protein, humanCDK2 protein, humanCIC-DUX4 fusion protein, humanCyclin-Dependent Kinase 2Cyclin EETV4 protein, humanOncogene ProteinsOncogene Proteins, FusionProto-Oncogene Proteins c-etsCancerMolecular geneticsOncology

Identifiers

PMID31329165
PMCPMC6668665
OpenAlexW2964288853

What OpenQuestion holds

Textmetadata
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.