Evidence map›Paper›PMID 41044182›Full record

ArticleNature communications2025

SFPQ-TFE3 reciprocally regulates mTORC1 and induces lineage plasticity in a mouse model of renal tumorigenesis.

Kaushal Asrani, Adrianna Amaral, Juhyung Woo, Sanaz Nourmohammadi Abadchi, Thiago Vidotto, Eddie Imada, Alyza Skaist, Kewen Feng, Hans B Liu, Mithila Kasbe and 10 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. Review
  2. Article
  3. Cancers · 2026
    Review
4 · The record

Corrections and comments

  • Update of
    2024
5 · Who and what money

Authors and funding

20 authors.

Kaushal Asrani *Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. kasrani1@jhmi.edu.ORCID http://orcid.org/0000-0002-9777-5296
Adrianna Amaral *Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID http://orcid.org/0000-0001-8771-7001
Juhyung WooDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Sanaz Nourmohammadi AbadchiDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Thiago VidottoDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Eddie ImadaDepartment of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Alyza SkaistDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Kewen FengDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Hans B LiuDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Mithila KasbeDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Yorifumi SatouDivision of Genomics and Transcriptomics, Kumamoto University, Kumamoto, Japan.ORCID http://orcid.org/0000-0002-1495-7810
Masaya BabaDepartment of Urology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.ORCID http://orcid.org/0000-0002-5308-6683
Yuichi OikeDepartment of Molecular Genetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.ORCID http://orcid.org/0000-0003-3245-5395
Patricia OutedaUniversity of Maryland, School of Medicine, Baltimore, MD, USA.
Terry WatnickUniversity of Maryland, School of Medicine, Baltimore, MD, USA.
Avi Z RosenbergDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Laura S SchmidtUrologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-5050-5491
W Marston LinehanUrologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0001-7983-3109
Pedram ArganiDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Tamara L LotanDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. tlotan1@jhmi.edu.ORCID http://orcid.org/0000-0002-0494-9067

Funding

Translational Research Central ServicesP30CA006973 · JOHNS HOPKINS UNIVERSITY · 1985 to 2025
$45.1M
PKD Innovation and Resource Development CoreU54DK126114 · UNIVERSITY OF MARYLAND BALTIMORE · 2025 to 2025
$954k
NCI NIH HHS HHSN261201500003CNCI NIH HHS HHSN261201500003INCI NIH HHS P30 CA006973NIDDK NIH HHS U54 DK126114
6 · The paper itself

Abstract

MiT/TFE gene fusions like SFPQ-TFE3 drive both epithelial (translocation RCC) and mesenchymal (PEComas) neoplasms. However, no mouse models for SFPQ-TFE3-related tumors exist and the underlying mechanisms of lineage plasticity remain unclear. Here, we demonstrate that constitutive murine renal expression of SFPQ-TFE3 disrupts kidney development with early neonatal renal failure and death, while post-natal induction induces infiltrative epithelioid tumors, that morphologically and transcriptionally resemble human PEComas, with strong activation of mTORC1 signaling via increased V-ATPase expression. Remarkably, SFPQ-TFE3 expression is sufficient to induce lineage plasticity, with down-regulation of the PAX2/PAX8 nephric lineage factors and tubular epithelial markers, and up-regulation of PEComa differentiation markers in transgenic mice, cell lines and human tRCC. mTOR inhibition downregulates SFPQ-TFE3 expression and rescues PAX8 expression and transcriptional activity in vitro. These data provide evidence of an epithelial cell-of-origin for TFE3-driven PEComas, highlighting a reciprocal role for SFPQ-TFE3 and mTOR in driving lineage plasticity in the kidney.

Indexed as

Basic Helix-Loop-Helix Leucine Zipper Transcription FactorsCarcinogenesisKidney NeoplasmsMechanistic Target of Rapamycin Complex 1Oncogene Proteins, FusionPTB-Associated Splicing FactorAnimalsCell LineageCell Line, TumorDisease Models, AnimalGene Expression Regulation, NeoplasticHumansKidneyMiceMice, TransgenicPAX2 Transcription FactorBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsMechanistic Target of Rapamycin Complex 1Oncogene Proteins, FusionPAX2 Transcription FactorPax8 protein, mousePAX8 Transcription FactorPTB-Associated Splicing FactorTcfe3 protein, mouseTFE3 protein, human

Identifiers

PMID41044182
PMCPMC12494988

What Socratic 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 Socratic graph.