Targeting Intratumoral Copper Inhibits Tumor Progression via p62-Mediated EZH2 Degradation and Potentiates Anti-PD-1 Immunotherapy in Oral Squamous Cell Carcinoma.

ABSTRACT: High copper levels are required for tumor initiation and progression, termed cuproplasia. However, its role and underlying mechanisms in oral squamous cell carcinoma (OSCC) remain poorly understood. It is find that copper and its transporter SLC31A1 accumulate extensively in OSCC. Blocking copper influx through SLC31A1 siRNA or copper chelators significantly represses OSCC both in vitro and in vivo. Single-cell RNA sequencing and multiplex immunohistochemical staining revealed that copper chelators specifically decrease the stem-like tumor epithelial cell subpopulation. Further investigation shows that intratumoral copper depletion reduces histone methyltransferase EZH2 expression at the protein level, but not at the mRNA level, as determined through a screen analysis of histone-modificati

SUBMITTER: Lin X 

PROVIDER: S-EPMC12561351 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature