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

IF 2.5 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Prostate Pub Date : 2025-10-01 DOI:10.1002/pros.70049

Zhe Tang, Peichao Guo, Yuanhua Liu

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引用次数: 0

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

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通过p53信号通路抑制糖酵解，LIAS促进前列腺癌细胞cuprotic。

背景：铜体增生在优化癌症治疗策略方面具有重要的潜力。然而，硫辛酸合成酶（LIAS）调控前列腺癌（PC）铜增生的分子机制尚不清楚。方法：利用GEPIA在线工具和PC细胞系分析LIAS在PC中的表达。采用cu2 +检测试剂盒、Western blot （LIAS/FDX1）和免疫荧光（DLAT寡聚化）评估cu2 +的特性。用CCK-8和菌落形成法测定细胞活力和增殖能力。采用qPCR检测p53通路基因表达。通过测量细胞外酸化率（ECAR）、葡萄糖摄取和ATP水平来分析糖酵解活性。在铜增生模型中使用糖酵解抑制剂验证了这种调节关系。结果：在PC和铜突模型中，LIAS的表达均显著下调。过表达LIAS可增强cuprotosis效应，抑制癌细胞的生存能力和增殖能力。进一步分析显示，LIAS通过激活p53途径抑制糖酵解，表现为细胞外酸化率（ECAR）降低、葡萄糖摄取减少和ATP水平降低。值得注意的是，糖酵解的抑制促进了铜增生，从而阻碍了肿瘤的进展。结论：LIAS通过激活p53信号通路抑制糖酵解活性，促进PC细胞铜化，抑制癌细胞增殖。这些发现表明，LIAS是干预PC的潜在治疗靶点，调节糖酵解-铜增生轴可能是改善PC进展的有效策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Prostate 医学-泌尿学与肾脏学

CiteScore

5.10

自引率

3.60%

发文量

180

审稿时长

1.5 months

期刊介绍： The Prostate is a peer-reviewed journal dedicated to original studies of this organ and the male accessory glands. It serves as an international medium for these studies, presenting comprehensive coverage of clinical, anatomic, embryologic, physiologic, endocrinologic, and biochemical studies.