Evidence map›Paper›PMID 41390483›Full record

ArticleNature communications2025

APOBEC3 promotes squamous differentiation via IL-1A/AP-1 signaling.

Michael S Sturdivant, Andrew S Truong, Mi Zhou, Elliott D Toomer, Wolfgang Beckabir, John Raupp, Ujjawal Manocha, Ibardo A Zambrano, Hung-Jui Tan, Marc A Bjurlin and 7 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 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. Squamous-state excursions activate APOBEC3A in cancer.bioRxiv : the preprint server for biology · 2026
    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

17 authors.

Michael S Sturdivant *Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID http://orcid.org/0000-0002-0729-2275
Andrew S Truong *Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Mi ZhouLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID http://orcid.org/0000-0001-8144-3468
Elliott D ToomerLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Wolfgang BeckabirLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
John RauppLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Ujjawal ManochaLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Ibardo A ZambranoDepartment of Urology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Hung-Jui TanDepartment of Urology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Marc A BjurlinDepartment of Urology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Angela B SmithDepartment of Urology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Tracy L RoseLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Matthew I MilowskyLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID http://orcid.org/0000-0002-8965-8129
Sara E WobkerLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Kathryn H GessnerLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Jeffrey S DamrauerLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. jeffrey_damrauer@med.unc.edu.ORCID http://orcid.org/0000-0001-8148-0285
William Y KimLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. wykim@med.unc.edu.ORCID http://orcid.org/0000-0001-7922-2156

Funding

Virology Research Program (Program 4)P30CA016086 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Deborah F. Tate · 1985 to 2026
$201.5M
CANCER CELL BIOLOGY TRAINING PROGRAMT32CA071341 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI CHANNING J. DER, Yuliya Pylayeva-Gupta · 1996 to 2026
$5.0M
UNC Integrated Translational Oncology Program (UNC-iTOP)T32CA244125 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI WILLIAM Y. KIM, Jen Jen Yeh · 2019 to 2026
$3.9M
In vivo Assessment of Chemotherapy Remodeling of the Bladder Cancer Immune MicroenvironmentR01CA241810 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI KIM, WILLIAM Y., VINCENT, BENJAMIN G · 2020 to 2024
$2.9M
Targeting APOBEC3-induced squamous differentiation in bladder cancerR01CA292625 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI WILLIAM Y. KIM · 2025 to 2026
$1.0M
Effect of APOBEC3 on Bladder Cancer Biology and Response to ImmunotherapyF31CA247250 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI TRUONG, ANDREW · 2020 to 2022
$138k
The Mutagenic Effects of APOBEC3A and APOBEC3B in Urothelial CarcinomaF31CA281339 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI STURDIVANT, MICHAEL SEAN · 2024 to 2025
$75k
NCI NIH HHS F31 CA247250NCI NIH HHS F31 CA281339NCI NIH HHS P30 CA016086NCI NIH HHS R01 CA241810NCI NIH HHS R01 CA292625NCI NIH HHS T32 CA071341NCI NIH HHS T32 CA244125U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R01CA241810U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R01CA292625
6 · The paper itself

Abstract

The APOBEC3 family of RNA and single stranded DNA cytidine deaminases contribute prominently to the mutagenesis of certain cancers including urothelial carcinoma of the bladder (UC). Remarkably, up to 70% of mutations in UC are attributable to the mutagenic activity of the APOBEC3 deaminases. Despite this strong association, few functional studies have investigated APOBEC3's role in bladder cancer. We report a genetically engineered murine model with conditional knock out of Pten and Trp53 in addition to overexpression of mouse Apobec3 (UPPA). Analysis of bladder tumors from UPPA mice demonstrates that mA3 promotes tumor progression and squamous trans-differentiation. We establish that APOBEC3 promotes squamous differentiation through IL-1α and downstream activation of the AP-1 transcription factor. Bulk RNA-sequencing from human UC shows APOBEC3A as the only human APOBEC3 family member to correlate with squamous differentiation. Furthermore, single cell and spatial transcriptomics reinforces the role of APOBEC3A in fostering squamous trans-differentiation and promoting the emergence of a subpopulation of highly squamous epithelial cells. Our results demonstrate that mouse Apobec3 and human APOBEC3A promote squamous differentiation in urothelial carcinoma and that this trans-differentiation phenotype is mediated through IL-1α signaling, a target of FDA approved therapies for rheumatologic disease.

Indexed as

Carcinoma, Squamous CellCytidine DeaminaseInterleukin-1alphaTranscription Factor AP-1Urinary Bladder NeoplasmsAnimalsCell DifferentiationFemaleHumansMiceMice, KnockoutProteinsPTEN PhosphohydrolaseSignal TransductionTumor Suppressor Protein p53APOBEC3A protein, humanApobec3 protein, mouseCytidine DeaminaseInterleukin-1alphaProteinsPTEN PhosphohydrolasePten protein, mouseTranscription Factor AP-1Trp53 protein, mouseTumor Suppressor Protein p53

Identifiers

PMID41390483
PMCPMC12789560

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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.