Evidence map›Paper›PMID 34329586›Full record

ArticleCancer cell2021

TRIM8 modulates the EWS/FLI oncoprotein to promote survival in Ewing sarcoma.

Bo Kyung A Seong, Neekesh V Dharia, Shan Lin, Katherine A Donovan, Shasha Chong, Amanda Robichaud, Amy Conway, Amanda Hamze, Linda Ross, Gabriela Alexe and 11 more

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

Article in Cancer cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.

0numbers the graph read from it
0cells of the map it votes in
76citing papers in PubMed
6.9field-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

76 citing papers in PubMed, 111 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. RNF168 promotes chronic colitis through ANXA7-mediated autophagy and NLRP3-driven pyroptosis.Apoptosis : an international journal on programmed cell death · 2026
    Article
  16. Article
  17. Article
  18. Disruption of Microhomology-mediated End-joining in Ewing Sarcoma.bioRxiv : the preprint server for biology · 2025
    Article
  19. Review
  20. Article

16 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

21 authors at 5 institutions in 2 countries.

Bo Kyung A SeongDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Neekesh V DhariaDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; The Broad Institute of MIT and Harvard, Cambridge, MA, USA; Division of Pediatric Hematology/Oncology, Boston Children's Hospital, Boston, MA, USA.
Shan LinDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Katherine A DonovanDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA.
Shasha ChongDepartment of Molecular and Cell Biology, University of California, Berkeley, CA, USA; Howard Hughes Medical Institute, University of California, Berkeley, CA, USA.
Amanda RobichaudDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Amy ConwayDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Amanda HamzeDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Linda RossDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Gabriela AlexeDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Biniam AdaneDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Behnam NabetDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA.
Fleur M FergusonDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA.
Björn StolteDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Dr.von Hauner Children's Hospital, Department of Pediatrics, University Hospital, LMU Munich, Munich, Germany.
Emily Jue WangDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Jialin SunDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA.
Xavier DarzacqDepartment of Molecular and Cell Biology, University of California, Berkeley, CA, USA; CIRM Center of Excellence, University of California, Berkeley, CA, USA.
Federica PiccioniThe Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Nathanael S GrayDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA.
Eric S FischerDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA.
Kimberly StegmaierDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; The Broad Institute of MIT and Harvard, Cambridge, MA, USA; Division of Pediatric Hematology/Oncology, Boston Children's Hospital, Boston, MA, USA. Electronic address: kimberly_stegmaier@dfci.harvard.edu.
Broad Institute · USDana-Farber Cancer Institute · USHarvard University · USHoward Hughes Medical Institute · USUniversity of California, Berkeley · US

Funding

The Center for Therapeutic Targeting of EWS-oncoproteinsU54CA231637 · NCI · DANA-FARBER CANCER INST · PI ARMSTRONG, SCOTT A, STEGMAIER, KIMBERLY · 2018 to 2022
$13.2M
Integrating Transforming Approaches to Identify and Target New Vulnerabilities in CancerR35CA210030 · NCI · DANA-FARBER CANCER INST · PI STEGMAIER, KIMBERLY · 2016 to 2022
$7.3M
Project 2: Evaluating the dynamic protein-protein interactions mediated by LCDs within EWS/FLI and its partners in living cells via single molecule imagingU54CA231641 · NCI · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · PI LESSNICK, STEPHEN L. · 2018 to 2018
$6.2M
Dissecting the Pathogenesis of Ewing Sarcoma with Integrative GenomicsR01CA204915 · NCI · DANA-FARBER CANCER INST · PI STEGMAIER, KIMBERLY, SWEET-CORDERO, ERIC ALEJANDRO · 2017 to 2021
$2.7M
NCI NIH HHS R01 CA204915NCI NIH HHS R35 CA210030NCI NIH HHS U54 CA231637NCI NIH HHS U54 CA231641
6 · The paper itself

Abstract

Fusion-transcription factors (fusion-TFs) represent a class of driver oncoproteins that are difficult to therapeutically target. Recently, protein degradation has emerged as a strategy to target these challenging oncoproteins. The mechanisms that regulate fusion-TF stability, however, are generally unknown. Using CRISPR-Cas9 screening, we discovered tripartite motif-containing 8 (TRIM8) as an E3 ubiquitin ligase that ubiquitinates and degrades EWS/FLI, a driver fusion-TF in Ewing sarcoma. Moreover, we identified TRIM8 as a selective dependency in Ewing sarcoma compared with >700 other cancer cell lines. Mechanistically, TRIM8 knockout led to an increase in EWS/FLI protein levels that was not tolerated. EWS/FLI acts as a neomorphic substrate for TRIM8, defining the selective nature of the dependency. Our results demonstrate that fusion-TF protein stability is tightly regulated and highlight fusion oncoprotein-specific regulators as selective therapeutic targets. This study provides a tractable strategy to therapeutically exploit oncogene overdose in Ewing sarcoma and potentially other fusion-TF-driven cancers.

Indexed as

Bone NeoplasmsCarrier ProteinsCell Line, TumorCell ProliferationCell SurvivalGene Knockout TechniquesHEK293 CellsHumansMicrofilament ProteinsNerve Tissue ProteinsOncogene Proteins, FusionProtein StabilityProteolysisProto-Oncogene Protein c-fli-1RNA-Binding Protein EWSSarcoma, EwingCarrier ProteinsEWS-FLI fusion proteinEWSR1 protein, humanFLI1 protein, humanFLII protein, humanMicrofilament ProteinsNerve Tissue ProteinsOncogene Proteins, FusionProto-Oncogene Protein c-fli-1RNA-Binding Protein EWSTrans-ActivatorsTRIM8 protein, humanE3 ligasesEwing sarcomaEWS/FLIfusion oncoproteinsneomorphic substrateoncogene overdoseprotein degradationTRIM8tumor dependencyubiquitination

Identifiers

PMID34329586
PMCPMC8443273
OpenAlexW3186057676

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.