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脂肪细胞导向外体的肝乳沟通驱动着原发性乳腺癌的进展

Chunni Li¹, Yiwen Lu¹, Yihong Li¹

¹Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China; Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China.

Cell metabolism

|September 25, 2025

概括

非酒精性脂肪肝 (NAFLD) 增加了乳腺癌的风险. 脂肪肝外基因组通过改变脂肪细胞代谢来促进瘤生长,揭示了肝乳沟通通路径的关键性.

科学领域:

肝病学肝病学是一种肝病学.
在瘤学瘤学.
代谢研究的研究.

背景情况:

非酒精性脂肪肝 (NAFLD) 与肝癌发病率的增加有关,但潜在的机制尚不清楚.
在NAFLD和乳腺癌风险增加之间存在相关性,特别是在异型增生症和预后不佳的患者中.

研究的目的:

阐明NAFLD促进乳腺癌发展的机制.
研究脂肪肝产生的外体在促进亲瘤性乳腺微观环境中的作用.

主要方法:

利用脂肪肝疾病和乳腺癌的小鼠模型.
分析了脂肪细胞中的外体积累,并确定了关键的分子相互作用 (ErbB4-Nrg4).
研究了tRNA甲基转移酶10同类C (TRMT10C) 在外体内的功能及其对线粒体基因表达 (ND5,ND6) 的影响.

主要成果:

脂肪肝外基因组优先积聚在乳腺脂肪细胞中,从而创造了一个亲瘤的微环境.
外体ErbB4与Nrg4结合调解脂肪细胞热流.
外体体中的TRMT10C修改了脂肪细胞中的线粒体mRNA翻译,增加了活性氧物种和自由脂肪酸的释放,从而推动了瘤的生长.
血ErbB4+外体的升高是NAFLD乳腺癌患者的独立预后标志物.

结论:

由脂肪肝外体驱动的新型肝乳代谢轴有助于乳腺癌的进展.
从肝脏到乳腺脂肪细胞的外体传播是NAFLD相关瘤发生的重要途径.
血ErbB4+外基因组具有作为伴并发性NAFLD和乳腺癌的预后生物标志物的潜力.

关键词:

N(1) 甲基氨酸氨基酸.脂肪细胞的脂肪细胞.乳腺癌乳腺癌乳腺癌在外基因组中,外基因组是外基因组.非酒精性脂肪性肝病是什么?

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