Evidence map›Paper›PMID 39046873›Full record

ArticleCell reports2024

PAI-1 uncouples integrin-β1 from restrain by membrane-bound β-catenin to promote collagen fibril remodeling in obesity-related neoplasms.

Li-Ling Lin, Bijaya Nayak, Pawel A Osmulski, Exing Wang, Chen-Pin Wang, Philip T Valente, Chiou-Miin Wang, Xi Tan, Nalini Santanam, Tian-Li Wang and 4 more

Abstract read
In one paragraph

Article in Cell reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing 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

9 citing papers in PubMed.

  1. Article
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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

14 authors.

Li-Ling LinDepartment of Molecular Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
Bijaya NayakDepartment of Molecular Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
Pawel A OsmulskiDepartment of Molecular Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
Exing WangCell Systems and Anatomy, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
Chen-Pin WangDepartment of Population Health Sciences, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
Philip T ValenteDepartment of Pathology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
Chiou-Miin WangDepartment of Molecular Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
Xi TanDepartment of Molecular Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
Nalini SantanamDepartment of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25701, USA.
Tian-Li WangDepartments of Pathology and Gynecology/Obstetrics, The Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Maria E GaczynskaDepartment of Molecular Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
Edward R KostDepartment of Obstetrics and Gynecology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
Tim H-M HuangDepartment of Molecular Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA. Electronic address: huangt3@uthscsa.edu.
Nameer B KirmaDepartment of Molecular Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA. Electronic address: kirma@uthscsa.edu.

Funding

TISSUE CULTURE---COREP30CA054174 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Robin Jean Leach · 1991 to 2026
$59.1M
PAI-1-mediated early-onset endometrial cancerR01CA257391 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI HUANG, TIM H.-M., KIRMA, NAMEER · 2021 to 2025
$2.1M
NCI NIH HHS P30 CA054174NCI NIH HHS R01 CA257391
6 · The paper itself

Abstract

The paracrine actions of adipokine plasminogen activator inhibitor-1 (PAI-1) are implicated in obesity-associated tumorigenesis. Here, we show that PAI-1 mediates extracellular matrix (ECM) signaling via epigenetic repression of DKK1 in endometrial epithelial cells (EECs). While the loss of DKK1 is known to increase β-catenin accumulation for WNT signaling activation, this epigenetic repression causes β-catenin release from transmembrane integrins. Furthermore, PAI-1 elicits the disengagement of TIMP2 and SPARC from integrin-β1 on the cell surface, lifting an integrin-β1-ECM signaling constraint. The heightened interaction of integrin-β1 with type 1 collagen (COL1) remodels extracellular fibrillar structures in the ECM. Consequently, the enhanced nanomechanical stiffness of this microenvironment is conducive to EEC motility and neoplastic transformation. The formation of extensively branched COL1 fibrils is also observed in endometrial tumors of patients with obesity. The findings highlight PAI-1 as a contributor to enhanced integrin-COL1 engagement and extensive ECM remodeling during obesity-associated neoplastic development.

Indexed as

beta CateninExtracellular MatrixIntegrin beta1ObesityPlasminogen Activator Inhibitor 1AnimalsCell MembraneCollagenCollagen Type IEndometrial NeoplasmsEndometriumEpithelial CellsFemaleHumansIntercellular Signaling Peptides and ProteinsOsteonectinbeta CateninCollagenCollagen Type IDKK1 protein, humanIntegrin beta1Intercellular Signaling Peptides and ProteinsOsteonectinPlasminogen Activator Inhibitor 1SERPINE1 protein, humanTissue Inhibitor of Metalloproteinase-2collagen fibrilsCP: CancerCP: MetabolismDKK1ECM remodelingendometrial cancerintegrin inside-out signalingobesityPAI-1

Identifiers

PMID39046873
PMCPMC11956528

What OpenQuestion holds

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LicenceCC BY-NC-ND
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.