A non-canonical EZH2/TRIM28 epigenetic axis drives heparan sulfate remodeling and melanoma metastasis.

ABSTRACT: Melanoma progression and metastasis are driven not only by oncogenic alterations but also by epigenetic programs that dynamically remodel the tumor microenvironment. Heparan sulfate (HS) proteoglycans are key extracellular matrix components that integrate growth factor signaling, cell-matrix interactions, and migratory behavior by controlling ligand availability and receptor engagement, yet how chromatin-associated factors regulate HS remodeling in cancer remains poorly defined. Here, we identify the histone methyltransferase EZH2 as a key regulator of HS biosynthesis in melanoma. Integrated bioinformatic and genomic analyses revealed enrichment of EZH2 and additional Polycomb Repressive Complex (PRC) factors at regulatory regions of HS biosynthetic genes. CRISPR-mediated loss of EZH2 alte

SUBMITTER: Patel NG 

PROVIDER: S-EPMC12871662 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature