PRC2 loss drives MPNST metastasis and matrix remodeling

Qierra R Brockman; Amanda Scherer; Gavin R McGivney; Wade R Gutierrez; Andrew P Voigt; Alexandra L Isaacson; Emily A Laverty; Grace Roughton; Vickie Knepper-Adrian; Benjamin Darbro; Munir R Tanas; Christopher S Stipp; Rebecca D Dodd

doi:10.1172/jci.insight.157502

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PRC2 loss drives MPNST metastasis and matrix remodeling

Journal article

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Peer reviewed

PRC2 loss drives MPNST metastasis and matrix remodeling

Qierra R Brockman, Amanda Scherer, Gavin R McGivney, Wade R Gutierrez, Andrew P Voigt, Alexandra L Isaacson, Emily A Laverty, Grace Roughton, Vickie Knepper-Adrian, Benjamin Darbro, …

JCI insight, Vol.7(20), e157502

09/06/2022

DOI: 10.1172/jci.insight.157502

PMCID: PMC9714789

PMID: 36066973

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Abstract

The histone methyltransferase PRC2 plays a complex role in cancer. Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive sarcomas with frequent loss-of-function mutations in PRC2 that are associated with poor outcome. Here, we identify a critical role for PRC2 loss in driving MPNST metastasis. PRC2-dependent metastatic phenotypes included increased collagen-dependent invasion, upregulation of matrix-remodeling enzymes, and elevated lung metastasis in orthotopic mouse models. Furthermore, clinical sample analysis determined that PRC2 loss correlated with metastatic disease, increased fibrosis, and decreased survival in patients with MPNSTs. These results may have broad implications for PRC2 function across multiple cancers and provide a strong rationale for investigating potential therapies targeting ECM-remodeling enzymes and tumor fibrosis to improve outcomes in patients with MPNSTs.

Details

Title: Subtitle: PRC2 loss drives MPNST metastasis and matrix remodeling
Creators: Qierra R Brockman
Amanda Scherer
Gavin R McGivney
Wade R Gutierrez
Andrew P Voigt
Alexandra L Isaacson
Emily A Laverty
Grace Roughton
Vickie Knepper-Adrian
Benjamin Darbro
Munir R Tanas
Christopher S Stipp
Rebecca D Dodd
Resource Type: Journal article
Publication Details: JCI insight, Vol.7(20), e157502
DOI: 10.1172/jci.insight.157502
PMID: 36066973
PMCID: PMC9714789
NLM abbreviation: JCI Insight
eISSN: 2379-3708
Grant note: DOI: 10.13039/100000048, name: American Cancer Society, award: Research Scholar Award (RDD); DOI: 10.13039/100000005, name: U.S. Department of Defense, award: NF170067, (RDD); DOI: 10.13039/100000002, name: National Institutes of Health, award: P30 CA086862, (UIowa)
Language: English
Date published: 09/06/2022
Academic Unit: Molecular Physiology and Biophysics; Microbiology and Immunology; Hematology, Oncology, and Blood & Marrow Transplantation; Stead Family Department of Pediatrics; The University of Iowa Institute for Vision Research; Pathology; Medical Genetics and Genomics; Biology; Internal Medicine
Record Identifier: 9984297158202771

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