Evidence map›Paper›PMID 40473600›Full record

ArticleNature communications2025

SWI/SNF ATPase silenced HLF potentiates lung metastasis in solid cancers.

Jin Zhou, Austin Hepperla, Jeremy M Simon, Kangsan Kim, Qing Hu, Chuanhai Zhang, Lei Dong, Lianxin Hu, Cheng Zhang, Chengheng Liao and 20 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. 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

30 authors.

Jin ZhouDepartment of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID http://orcid.org/0000-0002-0100-1983
Austin HepperlaLineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC, USA.ORCID http://orcid.org/0000-0002-0107-2001
Jeremy M SimonLineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC, USA.ORCID http://orcid.org/0000-0003-3906-1663
Kangsan KimDepartment of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Qing HuDepartment of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID http://orcid.org/0000-0002-3349-0056
Chuanhai ZhangDepartment of Physiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Lei DongQuantitative Biomedical Research Center, Department of Health Data Science and Biostatistics, Peter O'Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID http://orcid.org/0000-0001-9574-0148
Lianxin HuDepartment of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID http://orcid.org/0000-0001-5600-5634
Cheng ZhangDepartment of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Chengheng LiaoDepartment of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID http://orcid.org/0000-0002-9073-3835
Alice FangDepartment of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Yayoi AdachiDepartment of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Haoyong FuDepartment of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Tao WangDepartment of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Qian LiangDepartment of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Fangzhou ZhaoDepartment of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Hongyi LiuDepartment of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Masashi TakedaDepartment of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Jun FangDepartment of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Hua ZhongDepartment of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Peter LyDepartment of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID http://orcid.org/0000-0001-8946-7069
Lu WangDepartment of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.ORCID http://orcid.org/0000-0003-0441-0747
Payal KapurDepartment of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID http://orcid.org/0000-0002-4239-0495
Lin XuQuantitative Biomedical Research Center, Department of Health Data Science and Biostatistics, Peter O'Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID http://orcid.org/0000-0001-5815-4457
Liwei JiaDepartment of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Srinivas MalladiDepartment of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID http://orcid.org/0000-0002-0829-2365
James BrugarolasKidney Cancer Program, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID http://orcid.org/0000-0002-8575-499X
M Celeste SimonAbramson Family Cancer Research Institute, Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA, USA. celeste2@pennmedicine.upenn.edu.ORCID http://orcid.org/0000-0001-9106-447X
Bo LiDepartment of Biochemistry and Molecular Biology, Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, Guangzhou, PR China. libo47@smu.edu.cn.ORCID http://orcid.org/0000-0002-7979-8339
Qing ZhangDepartment of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA. Qing.Zhang@UTSouthwestern.edu.ORCID http://orcid.org/0000-0002-6595-8995

Funding

UT Southwestern Medical Center Simmons Comprehensive Cancer CenterP30CA142543 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI Kathryn Ann O'Donnell · 2010 to 2026
$53.7M
University of Texas Southwestern Medical Center SPORE in Kidney CancerP50CA196516 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI Payal Kapur, Payal Kapur · 2016 to 2026
$24.7M
Metabolic Tumor Suppressors in Renal Cancer: Unprecedented Roles in Disease ProgressionR35CA220483 · NCI · UNIVERSITY OF PENNSYLVANIA · PI M. CELESTE SIMON · 2017 to 2026
$9.4M
Role of BAP1/ASXL3 complex in transcriptional regulation and development-ADMIN SUPPL for EquipmentR35GM146979 · NIGMS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Lu Wang · 2022 to 2026
$2.2M
Exploration of ZHX2 as a novel substrate of pVHL and an oncogenic driver of renal cancerR01CA211732 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI ZHANG, QING · 2017 to 2021
$2.1M
Genome-wide CRISPR screening identifies critical regulators controlling ccRCC lung metastasisR01CA294133 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI Qing Zhang · 2025 to 2026
$1.0M
Cancer Prevention and Research Institute of Texas (Cancer Prevention Research Institute of Texas) RR190058NCI NIH HHS P30 CA142543NCI NIH HHS P50 CA196516NCI NIH HHS R01 CA211732NCI NIH HHS R01 CA294133NCI NIH HHS R35 CA220483NIGMS NIH HHS R35 GM146979U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) P50CA196516U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R01CA211732
6 · The paper itself

Abstract

Metastasis is the main cause of cancer-related deaths, yet the underlying mechanisms remain elusive. Here, using clear cell renal cell carcinoma (ccRCC), a tumor type with frequent lung metastases, we conduct an in vivo genome-wide CRISPR-Cas9 screen and identify HLF as a potent suppressor of lung metastasis. HLF depletion enhances ccRCC cell migration and lung metastasis, whereas HLF overexpression abrogates these effects. In ccRCC patients, HLF expression is reduced at metastatic sites and associates with epigenetic silencing mediated by the SWI/SNF ATPase subunit BRG1. HLF levels negatively correlate with migration potential in collagen. Mechanistically, HLF regulates LPXN expression, modulating the integration of collagen's mechanical cues with the actin cytoskeleton through Paxillin, thereby suppressing cancer cell migration and lung metastasis. Overexpression of HLF or pharmacological inhibition of BRG1 reduces cell invasion across multiple cancer types. Our findings suggest that targeting the BRG1-HLF axis offers a promising therapeutic strategy for combating metastatic cancers.

Indexed as

Carcinoma, Renal CellDNA HelicasesKidney NeoplasmsLung NeoplasmsNuclear ProteinsTranscription FactorsAnimalsCell Line, TumorCell MovementCRISPR-Cas SystemsFemaleGene Expression Regulation, NeoplasticGene SilencingHumansMiceDNA HelicasesNuclear ProteinsSMARCA4 protein, humanTranscription Factors

Identifiers

PMID40473600
PMCPMC12141477

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.