摘要
双硫死亡(disulfidptosis)是一种新型细胞死亡方式,由胱氨酸异常积累引发的二硫化物应激导致肌动蛋白骨架崩溃,其核心机制涉及溶质载体家族7成员11(solute carrier family 7 member 11,SLC7A11)高表达与葡萄糖代谢失衡的协同作用。研究显示,双硫死亡相关基因在乳腺癌中呈现显著异质性表达,其与乳腺癌亚型、免疫微环境重塑及血管生成调控存在深度关联。基于多组学数据构建的预后模型可有效预测患者生存期,而关键调控因子的发现为免疫治疗增效提供了新靶点。目前,葡萄糖转运蛋白(glucose transporter,GLUT)抑制剂等靶向药物在临床前模型中展现出抗肿瘤潜力,但仍面临多种挑战。未来研究需整合单细胞测序与功能验证,探索多通路协同机制,推动代谢-免疫联合治疗策略的临床转化。
Disulfidptosis is a newly identified form of regulated cell death characterized by collapse of the actin cytoskeleton due to disulfide stress caused by abnormal accumulation of cystine.Its core mechanism involves the synergistic effect of solute carrier family 7 member 11(SLC7A11)overexpression and glucose metabolic imbalance.Studies have shown that disulfidptosis-related genes exhibit significant heterogeneity in breast cancer,closely associated with breast cancer subtypes,remodeling of the immune microenvironment,and regulation of angiogenesis.Prognostic models constructed based on multi-omics data can effectively predict patient survival,while the identification of key regulatory factors provides new targets for enhancing immunotherapy.At present,targeted drugs such as glucose transporter(GLUT)inhibitors have demonstrated anti-tumor potential in preclinical models,but multiple challenges remain.Future studies should integrate single-cell sequencing with functional validation to explore multi-pathway synergistic mechanisms and to promote the clinical translation of metabolism-immunity combination therapeutic strategies.
作者
冯意倩
赵昱博
高鸿雁
史含笑
李元栋
FENG Yiqian;ZHAO Yubo;GAO Hongyan;SHI Hanxiao;LI Yuandong(First Clinical School,Shanxi Medical University,Taiyuan 030001;Academy of Medical Sciences,Shanxi Medical University,Taiyuan 030001;Department of Breast Surgery,First Hospital of Shanxi Medical University,Taiyuan 030001,China)
出处
《临床与病理杂志》
2025年第5期596-604,共9页
Journal of Clinical and Pathological Research
基金
山西省科技厅科技成果转化引导专项(202204021301066)。
关键词
双硫死亡
乳腺癌
代谢
氧化还原反应
治疗
disulfidptosis
breast cancer
metabolism
redox reaction
therapy
