Evidence map›Paper›PMID 31668005›Full record

ArticleEMBO reports2019

Class I HDAC inhibitors enhance YB-1 acetylation and oxidative stress to block sarcoma metastasis.

Amal M El-Naggar, Syam Prakash Somasekharan, Yemin Wang, Hongwei Cheng, Gian Luca Negri, Melvin Pan, Xue Qi Wang, Alberto Delaidelli, Bo Rafn, Jordan Cran and 13 more

Erratum issuedOpen access · hybridAbstract read
In one paragraph

Article in EMBO reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 68 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
68citing papers in PubMed, 2 pooled it
4.6field-weighted citation impact, top 4% 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

68 citing papers in PubMed, 2 syntheses or guidelines pooled it, 112 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. The histone deacetylase family in health and disease.Signal transduction and targeted therapy · 2026
    Review
  4. The Role of Long Noncoding RNAs in Modulation of Stress Granules in Cancer.Journal of cellular and molecular medicine · 2026
    Review
  5. Article
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  12. Review
  13. Article
  14. Article
  15. RNA-targeted proteomics identifies YBX1 as critical for efficient HCMV mRNA translation.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  16. Article
  17. Mechanisms of HDACs in cancer development.Frontiers in immunology · 2025
    Review
  18. Review
  19. Pharmacologic Inhibition of EIF4A Blocks NRF2 Synthesis to Prevent Osteosarcoma Metastasis.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024
    Article
  20. BML-281 promotes neuronal differentiation by modulating Wnt/CaMolecular and cellular biochemistry · 2024
    Article

8 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

23 authors at 6 institutions in 4 countries.

Amal M El-NaggarDepartment of Pathology & Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.ORCID 0000-0002-3202-6171
Syam Prakash SomasekharanVancouver Prostate Centre, Vancouver, BC, Canada.ORCID 0000-0002-9006-8206
Yemin WangDepartment of Molecular Oncology, BC Cancer, part of the Provincial Health Services Authority, Vancouver, BC, Canada.
Hongwei ChengVancouver Prostate Centre, Vancouver, BC, Canada.
Gian Luca NegriMichael Smith Genome Sciences Centre, Vancouver, BC, Canada.
Melvin PanDepartment of Molecular Oncology, BC Cancer, part of the Provincial Health Services Authority, Vancouver, BC, Canada.
Xue Qi WangDepartment of Molecular Oncology, BC Cancer, part of the Provincial Health Services Authority, Vancouver, BC, Canada.
Alberto DelaidelliDepartment of Pathology & Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.
Bo RafnDepartment of Molecular Oncology, BC Cancer, part of the Provincial Health Services Authority, Vancouver, BC, Canada.
Jordan CranDepartment of Molecular Oncology, BC Cancer, part of the Provincial Health Services Authority, Vancouver, BC, Canada.
Fan ZhangVancouver Prostate Centre, Vancouver, BC, Canada.
Haifeng ZhangDepartment of Pathology & Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.
Shane ColborneMichael Smith Genome Sciences Centre, Vancouver, BC, Canada.
Martin GleaveVancouver Prostate Centre, Vancouver, BC, Canada.ORCID 0000-0003-4235-0167
Anna MandinovaBrigham and Women's Hospital, Harvard University, Boston, MA, USA.
Nancy KedershaMassachusetts General Hospital, Harvard University, Boston, MA, USA.
Christopher S HughesDepartment of Molecular Oncology, BC Cancer, part of the Provincial Health Services Authority, Vancouver, BC, Canada.
Didier SurdezCentre de recherche de l'Institut Curie, Paris, France.
Olivier DelattreCentre de recherche de l'Institut Curie, Paris, France.
Yuzhuo WangVancouver Prostate Centre, Vancouver, BC, Canada.ORCID 0000-0002-9749-8591
David G HuntsmanDepartment of Pathology & Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.
Gregg B MorinMichael Smith Genome Sciences Centre, Vancouver, BC, Canada.
Poul H SorensenDepartment of Pathology & Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.ORCID 0000-0001-7447-2199
Provincial Health Services Authority · CAUniversity of British Columbia · CACanada's Michael Smith Genome Sciences Centre · CAInstitut Curie · FRBrigham and Women's Hospital · USHarvard University · US

Funding

The Tumor Suppressor Role of SMARCA4 in SCCOHTR01CA195670 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI HUNTSMAN, DAVID, TRENT, JEFFREY M. · 2015 to 2019
$3.7M
Gouvernement du Canada|Canadian Institutes of Health Research (CIHR) 143280Michael Smith Foundation for Health Research (MSFHR) 17159Terry Fox Research Institute (TFRI) 1021Terry Fox Research Institute (TFRI) 1062
6 · The paper itself

Abstract

Outcomes for metastatic Ewing sarcoma and osteosarcoma are dismal and have not changed for decades. Oxidative stress attenuates melanoma metastasis, and melanoma cells must reduce oxidative stress to metastasize. We explored this in sarcomas by screening for oxidative stress sensitizers, which identified the class I HDAC inhibitor MS-275 as enhancing vulnerability to reactive oxygen species (ROS) in sarcoma cells. Mechanistically, MS-275 inhibits YB-1 deacetylation, decreasing its binding to 5'-UTRs of NFE2L2 encoding the antioxidant factor NRF2, thereby reducing NFE2L2 translation and synthesis of NRF2 to increase cellular ROS. By global acetylomics, MS-275 promotes rapid acetylation of the YB-1 RNA-binding protein at lysine-81, blocking binding and translational activation of NFE2L2, as well as known YB-1 mRNA targets, HIF1A, and the stress granule nucleator, G3BP1. MS-275 dramatically reduces sarcoma metastasis in vivo, but an MS-275-resistant YB-1K81-to-alanine mutant restores metastatic capacity and NRF2, HIF1α, and G3BP1 synthesis in MS-275-treated mice. These studies describe a novel function for MS-275 through enhanced YB-1 acetylation, thus inhibiting YB-1 translational control of key cytoprotective factors and its pro-metastatic activity.

Indexed as

AcetylationAnimalsAntineoplastic AgentsBenzamidesBone NeoplasmsCell Line, TumorCells, CulturedHistone Deacetylase InhibitorsHumansHypoxia-Inducible Factor 1, alpha SubunitMiceNeoplasm MetastasisNF-E2-Related Factor 2Oxidative StressPyridinesSarcoma, EwingAntineoplastic AgentsBenzamidesentinostatHif1a protein, mouseHistone Deacetylase InhibitorsHypoxia-Inducible Factor 1, alpha SubunitNfe2l2 protein, mouseNF-E2-Related Factor 2PyridinesTranscription FactorsYbx1 protein, mouseHDAC inhibitorsmetastasisNRF2sarcomaYB-1

Identifiers

PMID31668005
PMCPMC6893361
OpenAlexW2982674222

What Socratic holds

Textmetadata
LicenceCC BY
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.