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无胚胎胚胎干细胞驱动着瘤转移的发生

Rong Xiao¹, Deshu Xu², Meili Zhang¹

¹State Key Laboratory of Common Mechanism Research for Major Diseases, Department of Medical Genetics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, 100005, China.

Nature communications

|February 5, 2024

概括

积体,一个异常的染色体数量,驱动癌症转移独立于基因突变. 向蛋白酶体活动和内质网膜应激抑制了这种形瘤的扩散.

科学领域:

在瘤学瘤学.
细胞生物学细胞生物学
遗传学遗传学是一个

背景情况:

对正常染色体数的偏差 - - 形积分,是癌症的常见特征.
高积体水平往往与癌症转移和患者的不良结果相关.
在癌症转移中血管积分症的因果作用需要进一步调查.

研究的目的:

为了调查动脉质在癌症转移中的因果作用.
确定形积分症促进瘤扩散的机制.
探索针对积体驱动转移的治疗策略.

主要方法:

使用无倍体和双倍体的小鼠胚胎干细胞 (ESCs) 形成瘤.
从外周血液中分离和描述循环瘤细胞.
初级瘤和转移的单细胞RNA测序.
蛋白质酶活性和内质网膜 (ER) 应激的分析.

主要成果:

体性ESC衍生的瘤,但不是双体的,转移到多个器官,没有额外的副本数变异或驱动突变.
体循环瘤细胞表现出增强的迁移和器官殖民能力.
单细胞RNA测序揭示了一种独特的高干细胞群体在阳化瘤和转移中.
形细胞在分化过程中表现出减少的蛋白酶体活性和增加的ER压力,损害蛋白质降解并导致分化缺陷.

结论:

单独的积体足以驱动癌症转移.
治疗药物如欧蛋白 (蛋白质酶激活剂) 和4-PBA (ER应激抑制剂) 可以有效地抑制形瘤转移.
了解形积分症引起的分化缺陷的机制为癌症治疗提供了新的治疗点.

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