PRC2 loss drives MPNST metastasis and matrix remodeling.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 36066973.
- Also identified by DOI 10.1172/jci.insight.157502 and PMC identifier 9714789.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- Neurofibrosarcoma