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乳酸线粒体氧化驱动了转移性乳腺癌的干细胞潜力

Jia-Jia Zhang¹, Ruo-Fei Tian¹, Chang-Geng Song²

¹Department of Cell Biology, National Translational Science Center for Molecular Medicine, Fourth Military Medical University; State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Xi'an, P.R. China.

Nature communications

|December 18, 2025

概括

转移性乳腺癌细胞使用乳酸来维持干和扩散. 使用线粒体CD147/MCT1/LDHB复合体的线粒体CD147/MCT1/LDHB复合体的向抑制了转移,提供了一个潜在的治疗策略.

科学领域:

癌症中的代谢重编程
癌症干细胞生物学
转移和癌症的进展.

背景情况:

转移性癌细胞表现出营养灵活性.
维持转移性癌症干细胞潜力的特定营养素在很大程度上是未知的.
了解这些代谢依赖关系对于开发向疗法至关重要.

研究的目的:

确定支持转移性乳腺癌细胞干细胞和转移的关键营养素.
阐明这种营养物质促进茎的分子机制.
评估针对这种代谢途径的新型治疗策略.

主要方法:

在脱离的转移性乳腺癌细胞中分析乳酸摄取和氧化.
对三酸循环和氧化酸化的研究.
通过α-KG-DNMT3B介导的SOX2低甲基化的评估.
对CD147/MCT1/LDHB复合体表达与患者瘤数据的相关性分析.
在体内研究使用细胞内表达的单链变量片段 (mito-CD147 scFv) 向线粒体CD147.

主要成果:

转移性乳腺癌细胞利用和氧化乳酸以保持干性并启动转移.
乳酸燃料三碳酸循环和氧化酸化,通过SOX2低甲基化增强茎状性.
线粒体CD147/MCT1/LDHB复合体对乳酸进口和氧化至关重要,与患者转移相关.
米托-CD147 scFv 治疗破坏了这个复杂的,抑制了干细胞,减少了循环中的瘤细胞,并减少了转移负担.

结论:

乳酸是维持转移性乳腺癌干和驱动转移的关键营养素.
线粒体CD147/MCT1/LDHB复合体是乳酸燃料转移的关键调解者.
准线粒体CD147是一种有前途的治疗方法,可以抑制乳腺癌患者的转移.

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