LRPPRC confers enhanced oxidative phosphorylation metabolism in triple-negative breast cancer and represents a therapeutic target

作者：Q. K. Xue, Wenxi Wang, Jie Liu, Dachi Wang, Tianyu Zhang, Tingting Shen, Xiangsheng Liu, Xiaojia Wang, Xiying Shao, Wei Zhou, Xiaohong Fang · 发表于：Journal of Translational Medicine · 年份：2025 · DOI：10.1186/s12967-024-05946-6 · 被引用次数：19 · 研究领域：Cell death mechanisms and regulation、Cancer, Hypoxia, and Metabolism、Mitochondrial Function and Pathology

BACKGROUND: Triple-negative breast cancer (TNBC) is a highly malignant tumor that requires effective therapeutic targets and drugs. Oxidative phosphorylation (OXPHOS) is a metabolic vulnerability of TNBC, but the molecular mechanism responsible for the enhanced OXPHOS remains unclear. The current strategies that target the electronic transfer function of OXPHOS cannot distinguish tumor cells from normal cells. Investigating the mechanism underlying OXPHOS regulation and developing corresponding therapy strategies for TNBC is of great significance. METHODS: Immunohistochemistry and sequencing data reanalysis were used to investigate LRPPRC expression in TNBC. In vitro and in vivo assays were applied to investigate the roles of LRPPRC in TNBC progression. RT-qPCR, immunoblotting, and Seahorse XF assay were used to examine LRPPRC's functions in the expression of OXPHOS subunits and energy metabolism. In vitro and in vivo functional assays were used to test the therapeutic effect of gossypol acetate (GAA), a traditional gynecological drug, on LRPPRC suppression and OXPOHS inhibition. RESULTS: LRPPRC was specifically overexpressed in TNBC. LRPPRC knockdown suppressed the proliferation, metastasis, and tumor formation of TNBC cells. LRPPRC enhanced OXPHOS metabolism by increasing the expression of OXPHOS complex subunits encoded by the mitochondrial genome. GAA inhibited OXPHOS metabolism by directly binding LRPPRC, causing LRPPRC degradation, and downregulating the expression of O...