DLST drives lung adenocarcinoma progression by modulating cuproptosis-related copper homeostasis and apoptosis via an EP300-dependent mechanism

Abstract

Highlights • DLST is significantly upregulated in lung adenocarcinoma (LUAD) and correlates with advanced clinical stage and poor prognosis, promoting tumor growth by increasing intracellular copper levels and modulating cuproptosis-related proteins (HSP70, SLC31A1).• Mechanistically, the EP300–DLST–DLD axis is identified as a key pathway where EP300 enhances DLST phosphorylation, and DLST exerts anti-apoptotic effects via upregulation of DLD, linking cuproptosis regulation to tumor progression.• Targeting DLST or the EP300–DLST–DLD axis represents a potential therapeutic strategy for LUAD, supported by in vivo tumor models and single-cell RNA-seq revealing co-expression in the tumor microenvironment.