LIAS Promotes Cuproptosis in Prostate Cancer Cells by Suppressing Glycolysis via the p53 Signaling Pathway

Cuproptosis holds significant potential for optimizing cancer therapeutic strategies. However, the molecular mechanism by which lipoic acid synthase (LIAS) regulates cuproptosis in prostate cancer (PC) remains unclear.

The GEPIA online tool and PC cell lines were used to analyze the expression of LIAS in PC. Cuproptosis characteristics were assessed using Cu²⁺ detection kits, Western blot (LIAS/FDX1), and immunofluorescence (DLAT oligomerization). Cell viability and proliferation capacity were determined by CCK-8 and colony formation assays. qPCR was used to detect p53 pathway gene expression. Glycolytic activity was analyzed by measuring extracellular acidification rate (ECAR), glucose uptake, and ATP levels. The regulatory relationship was validated using glycolytic inhibitors within the cuproptosis model.

LIAS expression was significantly downregulated in both PC and cuproptosis models. Overexpression of LIAS enhanced cuproptosis effects and suppressed the viability and proliferative capacity of cancer cells. Further analysis revealed that LIAS suppressed glycolysis by activating the p53 pathway, manifested by decreased extracellular acidification rate (ECAR), reduced glucose uptake, and diminished ATP levels. Notably, inhibition of glycolysis promoted cuproptosis, thereby impeding tumor progression.

LIAS promotes cuproptosis and inhibits cancer cell proliferation in PC by activating the p53 signaling pathway to suppress glycolytic activity. These findings indicate that LIAS represents a potential therapeutic target for intervening in PC, and regulation of the glycolysis-cuproptosis axis may serve as an effective strategy for improving PC progression.