在HGSOC中,ATF3的特征是具有侵略性的耐药性持久细胞
Kathrin Böpple1, Yaara Oren2, Whitney S Henry3
1Dr. Margarete Fischer-Bosch - Institute of Clinical Pharmacology and University of Tuebingen, Auerbachstr. 112, 70376, Stuttgart, Germany. Kathrin.Boepple@bosch-health-campus.com.
Cell death & disease
|April 24, 2024
概括
高度血清性卵巢癌 (HGSOC) 的耐药性持久细胞促进复发. 向压力标志物ATF3和上皮-介质细胞过渡 (EMT) 可以改善HGSOC患者的治疗反应和存活率.
科学领域:
- 在瘤学瘤学.
- 细胞生物学 细胞生物学
- 基因组学就是基因组学.
背景情况:
- 高度血清性卵巢癌 (HGSOC) 是最致命的亚型.
- 尽管初始基于的治疗,复发是常见的,通常是由于耐药性持续性 (DTP) 细胞.
研究的目的:
- 研究HGSOC中的DTP细胞的特征.
- 确定导致HGSOC复发的分子机制.
- 探索治疗目标,以克服治疗耐药性.
主要方法:
- 生成的同位素HGSOC克隆 (以前没有接受过治疗和耐受西斯).
- 在异种移植模型和患者样本中进行单细胞RNA测序.
- 分析了TCGA数据以求生存相关性.
主要成果:
- 从DTP衍生的细胞表现出改变的形态和增加的上皮介质转变 (EMT) 标志物.
- 激进的DTP细胞过度表达了压力标记ATF3;ATF3倒置增加了对西斯普拉丁的敏感性.
- 复发瘤和患者样本显示EMT和ER压力标志物增加,包括ATF3.
- 较低的ATF3相关的部分EMT基因表达与改善的无进展生存率相关.
结论:
- 增加ATF3表达和部分EMT有助于激进的DTP形成和HGSOC复发.
- 在HGSOC中,ATF3和EMT通路是克服西斯普拉丁耐药性的潜在治疗目标.
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