Evidence map›Paper›PMID 40347939›Full record

ArticleCell reports. Medicine2025

Suppressing proteasome activity enhances sensitivity to actinomycin D in diffuse anaplastic Wilms tumor.

Patricia D B Tiburcio, Kenian Chen, Lin Xu, Kenneth S Chen

Abstract read
In one paragraph

Article in Cell reports. Medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. 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

4 authors.

Patricia D B TiburcioDepartment of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Kenian ChenQuantitative Biomedical Research Center, Peter O'Donnell School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Lin XuDepartment of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Quantitative Biomedical Research Center, Peter O'Donnell School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Kenneth S ChenDepartment of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: kenneth.chen@utsouthwestern.edu.

Funding

TRANSLATIONAL AND ANALYTICAL CHEMISTRY COREP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI PETER W PISTERS · 1985 to 2026
$279.3M
UT Southwestern Medical Center Simmons Comprehensive Cancer CenterP30CA142543 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI Marcel Bernard Mettlen · 2010 to 2026
$53.7M
The role of PLAG1 in Wilms tumor formationK08CA207849 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI CHEN, KENNETH SUNG-MAN · 2017 to 2021
$781k
Functional Proteomics by Reverse Phase Protein Array in CancerR50CA221675 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI LU, YILING · 2017 to 2021
$726k
Identifying neuroblastoma drivers and bringing them to the clinicR21CA259771 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI SKAPEK, STEPHEN X, XU, LIN · 2021 to 2021
$437k
NCI NIH HHS K08 CA207849NCI NIH HHS P30 CA016672NCI NIH HHS P30 CA142543NCI NIH HHS R21 CA259771NCI NIH HHS R50 CA221675
6 · The paper itself

Abstract

Wilms tumor is the most common pediatric kidney cancer, and diffuse anaplastic Wilms tumor is the most chemoresistant subtype. Here, we explore how Wilms tumor cells evade the chemotherapy actinomycin D, which inhibits ribosomal RNA biogenesis. Using ribosome profiling, protein arrays, and a genome-wide knockout screen, we describe how actinomycin D disrupts protein homeostasis and blocks cell-cycle progression. When ribosomal capacity is limited by actinomycin D treatment, anaplastic Wilms tumor cells preferentially translate proteasome components. Next, we find that the proteasome inhibitor bortezomib sensitizes cells to actinomycin D treatment in vitro and prolongs survival in xenograft models. Lastly, increased levels of proteasome components are associated with anaplastic histology and worse prognosis in Wilms tumor patients. In sum, maintaining protein homeostasis is critical for Wilms tumor proliferation, and it can be therapeutically disrupted by blocking protein synthesis or turnover.

Indexed as

DactinomycinKidney NeoplasmsProteasome Endopeptidase ComplexWilms TumorAnimalsBortezomibCell Line, TumorCell ProliferationDrug Resistance, NeoplasmHumansMiceProteasome InhibitorsRibosomesXenograft Model Antitumor AssaysBortezomibDactinomycinProteasome Endopeptidase ComplexProteasome Inhibitorsactinomycin Dproteasomeprotein homeostasisWilms tumor

Identifiers

PMID40347939
PMCPMC12147910

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.