Evidence map›Paper›PMID 39894896›Full record

ArticleNature communications2025

The O-glycosyltransferase C1GALT1 promotes EWSR1::FLI1 expression and is a therapeutic target for Ewing sarcoma.

Shahid Banday, Alok K Mishra, Romana Rashid, Tianyi Ye, Amjad Ali, Junhui Li, Jason T Yustein, Michelle A Kelliher, Lihua Julie Zhu, Sara K Deibler and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. Article
  2. Review
  3. 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

12 authors.

Shahid BandayDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA. shahidkhursheed.banday@umassmed.edu.ORCID http://orcid.org/0000-0001-8539-6662
Alok K MishraDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA.ORCID http://orcid.org/0000-0002-7742-2426
Romana RashidDepartment of Medicine, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA.
Tianyi YeDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA.ORCID http://orcid.org/0000-0002-8242-5242
Amjad AliDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA.
Junhui LiDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA.ORCID http://orcid.org/0000-0003-3973-1700
Jason T YusteinWinship Cancer Institute and Aflac Cancer and Blood Disorders Center, Emory University, Atlanta, GA, 30322, USA.ORCID http://orcid.org/0000-0002-2052-0527
Michelle A KelliherDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA.ORCID http://orcid.org/0000-0001-9211-3659
Lihua Julie ZhuDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA.ORCID http://orcid.org/0000-0001-7416-0590
Sara K DeiblerDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA.
Sunil K MaloniaDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA. sunil.malonia@umassmed.edu.ORCID http://orcid.org/0000-0002-2727-5165
Michael R GreenDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA.ORCID http://orcid.org/0000-0003-3017-3298

Funding

Mechanism(s) of TAL-1/SCL-mediated LeukemogenesisR01CA096899 · NCI · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI MICHELLE ALICE KELLIHER · 2004 to 2026
$6.9M
NCI NIH HHS R01 CA096899
6 · The paper itself

Abstract

Ewing sarcoma (ES) is an aggressive bone cancer driven by the oncogenic fusion-protein EWSR1::FLI1, which is not present in normal cells and is therefore an attractive therapeutic target. However, as a transcription factor, EWSR1::FLI1 is considered undruggable. Factors that promote EWSR1::FLI1 expression, and thus whose inhibition would reduce EWSR1::FLI1 protein levels and function, are potential drug targets. Here, using genome-scale CRISPR/Cas9 knockout screening, we identify C1GALT1, a galactosyltransferase required for the biosynthesis of many O-glycoproteins, as a factor that promotes EWSR1::FLI1 expression. We show that C1GALT1 acts by O-glycosylating the pivotal Hedgehog (Hh) signaling component Smoothened (SMO), thereby stabilizing SMO and stimulating the Hh pathway, which we find directly activates EWSR1::FLI1 transcription. Itraconazole, an FDA-approved anti-fungal agent that is known to inhibit C1GALT1, reduces EWSR1::FLI1 levels in ES cell lines and suppresses growth of ES xenografts in mice. Our study reveals a therapeutically targetable mechanism that promotes EWSR1::FLI1 expression and ES tumor growth.

Indexed as

Bone NeoplasmsGalactosyltransferasesProto-Oncogene Protein c-fli-1RNA-Binding Protein EWSSarcoma, EwingAnimalsCell Line, TumorCRISPR-Cas SystemsGene Expression Regulation, NeoplasticHedgehog ProteinsHumansMiceOncogene Proteins, FusionSignal TransductionXenograft Model Antitumor Assaysbeta-1,4-galactosyltransferase IEWSR1 protein, humanGalactosyltransferasesHedgehog ProteinsOncogene Proteins, FusionProto-Oncogene Protein c-fli-1RNA-Binding Protein EWS

Identifiers

PMID39894896
PMCPMC11788431

What OpenQuestion holds

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Registered trials

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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.