Copper ionophore enhanced cisplatin efficiency through DLAT-cuprotosis

Area of Science:

• Oncology
• Molecular Biology
• Cancer Research

Background:

• Triple-negative breast cancer (TNBC) lacks effective treatments.
• Cuproptosis-related genes (CRGs) influence breast cancer progression.
• The role of dihydrolipoamide S-acetyltransferase (DLAT) in breast cancer is unclear.

Purpose of the Study:

• To investigate the role and mechanisms of DLAT in breast cancer.
• To explore DLAT's potential as a therapeutic target and biomarker.

Main Methods:

• Analysis of TCGA-BRCA and HAP databases for DLAT expression.
• Differential gene and enrichment analyses.
• DLAT knockdown experiments in breast cancer cells.
• Drug sensitivity assays and xenograft models with ES-Cu.

Main Results:

• DLAT expression is altered in breast tumors and linked to prognosis.
• Elevated DLAT is involved in cell cycle, senescence, and p53 pathways, correlating with immune infiltration.
• DLAT knockdown inhibits proliferation, migration, and invasion.
• ES-Cu reverses cisplatin resistance by inducing DLAT oligomerization, cuproptosis, and increasing ROS.

Conclusions:

• DLAT plays a significant role in breast cancer progression and chemoresistance.
• DLAT is a potential biomarker for immunotherapy and a mediator of cuproptosis.
• Targeting DLAT offers a promising strategy to enhance breast cancer chemotherapy efficacy.