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基因组甲基转移酶ASH1L主要转移,并在骨内的巨细胞的代谢重编程

Chenling Meng¹, Kevin Lin², Wei Shi¹

¹Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.

Nature communications

|May 20, 2025

概括

基隆甲基转移酶ASH1L通过重编程癌细胞和巨细胞驱动前列腺癌骨转移. 抑制ASH1L-HIF-1α-巨轴对抗转移治疗有希望.

科学领域:

在瘤学瘤学.
表观遗传学在表观遗传学中,表观遗传学是指表观遗传学.
癌症转移癌症转移

背景情况:

骨转移是癌症死亡的一个重要原因.
骨转移背后的表观遗传机制尚未完全理解.

研究的目的:

为了研究表观遗传调节器在前列腺癌骨转移中的作用.
确定治疗骨转移性疾病的新型治疗点.

主要方法:

基因分析以确定前列腺癌骨转移中的放大基因.
在体外和体外模型研究ASH1L的功能.
对基因组胺甲基化模式和基因表达的分析.
研究癌细胞和巨细胞之间的相互作用.
药理上抑制已识别的途径.

主要成果:

基因组甲基转移酶ASH1L是基因扩增的,对于前列腺癌骨转移至关重要.
ASH1L与HIF-1α结合,诱导癌细胞中的前转移性转录组.
这一过程促进单细胞分化为与脂质相关的巨细胞 (LA-TAMs),在骨中增强了前瘤表型.
鉴定出IGF-2是ASH1L/HIF-1α的直接标,它介导LA-TAM分化和代谢重编程.
在临床前模型中,ASH1L-HIF-1α-巨细胞轴的药理抑制显示出显著的抗转移效应.

结论:

癌细胞的表观遗传变化可以重编程细胞代谢和髓状细胞功能,以促进转移性生长.
ASH1L作为一个表观遗传驱动器,它启动转移,并影响骨内的巨细胞可塑性.
ASH1L-HIF-1α-巨细胞轴代表了转移性恶性瘤的一个有希望的治疗标.

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