前列腺癌中的神经内分泌过渡是动态的,并且依赖ASCL1的
Rodrigo Romero1, Tinyi Chu2, Tania J González-Robles3,4
1Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
bioRxiv : the preprint server for biology
|April 22, 2024
概括
血统可塑性驱动激进的神经内分泌前列腺癌 (NEPC),但需要特定的体内微环境. 了解ASCL1表达的时间是有效的前列腺癌治疗的关键.
科学领域:
- 在瘤学瘤学.
- 癌症生物学 癌症生物学
- 分子机制的分子机制
背景情况:
- 血统可塑性对于癌症的进展和治疗耐药性至关重要.
- 驱动神经内分泌前列腺癌 (NEPC) 血统转变的机制尚不清楚.
- 现有的有机体模型不能完全复制NEPC开发所需的体内微环境.
研究的目的:
- 为研究神经内分泌前列腺癌 (NEPC) 血统可塑性开发一个体内平台.
- 为了确定前列腺癌中神经内分泌转换的分子驱动因素.
- 调查微环境在血统可塑性中的作用.
主要方法:
- 工程小鼠前列腺器官的正位素移植.
- 带有驱动器改变的基因工程 (Rb1,Trp53,cMyc,Pten).
- 综合多重免疫光学,空间转录组学和PrismSpot分析.
主要成果:
- 在前列腺癌有机体中Rb1删除驱动 ASCL1+ NEPC 的进展.
- 血统过渡到NEPC需要一个本土的体内微环境.
- ASCL1+ NEPC 细胞源自 KRT8+ 发光性上皮细胞,转录异质性增加.
- 失去了Ascl1影响NEPC的进展和可塑性,影响AR表达和割敏感性.
结论:
- 针对血统可塑性的治疗方法的时间对于前列腺癌治疗至关重要.
- 该模型提供了一个平台,用于识别血统可塑性的新型驱动因素.
- 了解血统可塑性机制对于克服前列腺癌治疗阻力至关重要.
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