Evidence map›Paper›PMID 40451561›Full record

ArticleCellular signalling2025

Ewing sarcoma depends on C4orf48/NICOL, a NELL2 cofactor regulated by Hippo signaling.

Panneerselvam Jayabal, Xiuye Ma, Yidong Chen, Yaxia Yuan, Yuzuru Shiio

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cellular signalling, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

5 authors.

Panneerselvam JayabalGreehey Children's Cancer Research Institute, The University of Texas Health Science Center, San Antonio, TX 78229, USA.
Xiuye MaGreehey Children's Cancer Research Institute, The University of Texas Health Science Center, San Antonio, TX 78229, USA.
Yidong ChenGreehey Children's Cancer Research Institute, The University of Texas Health Science Center, San Antonio, TX 78229, USA; Department of Population Health Sciences, The University of Texas Health Science Center, San Antonio, TX 78229, USA; Mays Cancer Center, The University of Texas Health Science Center, San Antonio, TX 78229, USA.
Yaxia YuanMays Cancer Center, The University of Texas Health Science Center, San Antonio, TX 78229, USA; Department of Biochemistry and Structural Biology, The University of Texas Health Science Center, San Antonio, TX 78229, USA.
Yuzuru ShiioGreehey Children's Cancer Research Institute, The University of Texas Health Science Center, San Antonio, TX 78229, USA; Mays Cancer Center, The University of Texas Health Science Center, San Antonio, TX 78229, USA; Department of Biochemistry and Structural Biology, The University of Texas Health Science Center, San Antonio, TX 78229, USA. Electronic address: shiio@uthscsa.edu.

Funding

The role of the receptor complex and the cofactors in IGSF10 signalingU01CA283414 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI YUZURU SHIIO · 2024 to 2026
$1.0M
The role of the receptor complex and the cofactors in IGSF10 signalingR01CA283414 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI SHIIO, YUZURU · 2023 to 2023
$355k
NCI NIH HHS R01 CA283414NCI NIH HHS U01 CA283414
6 · The paper itself

Abstract

Ewing sarcoma is a cancer of bone and soft tissue in children characterized by a chromosomal translocation that fuses EWS and an ETS family transcription factor, most commonly FLI1. EWS-FLI1 is the driver of this cancer. Using secretome proteomics and molecular cell biology, we found that FAT4, an atypical cadherin activating Hippo signaling, is a transcriptional target of EWS-FLI and is a dependency in Ewing sarcoma. We determined that FAT4 - Hippo signaling regulates the expression of a secreted polypeptide, C4orf48/NICOL. We demonstrate that Ewing sarcoma depends on C4orf48, which functions as a cofactor for NELL2, a cytokine we previously identified as a critical dependency in Ewing sarcoma. These results reveal C4orf48 as a targetable dependency that links FAT4 - Hippo signaling and NELL2 signaling in Ewing sarcoma.

Indexed as

Nerve Tissue ProteinsProtein Serine-Threonine KinasesSarcoma, EwingSignal TransductionCadherinsCell Line, TumorGene Expression Regulation, NeoplasticHippo Signaling PathwayHumansOncogene Proteins, FusionProto-Oncogene Protein c-fli-1RNA-Binding Protein EWSCadherinsEWS-FLI fusion proteinNerve Tissue ProteinsOncogene Proteins, FusionProtein Serine-Threonine KinasesProto-Oncogene Protein c-fli-1RNA-Binding Protein EWSC4orf48Ewing sarcomaFAT4Hippo signalingNELL2NICOLSecretome

Identifiers

PMID40451561
PMCPMC13008417

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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.