在胰腺恒温和致癌过程中,细胞的克隆扩张
Patrick Neuhöfer1,2,3, Caitlin M Roake1,2,3, Stewart J Kim1,2,3
1Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
Nature
|September 16, 2021
概括
罕见的胰腺细胞表达高水平的逆转录酶 (TERT) 驱动胰腺癌的发病. 这些高TERT细胞在发生突变时形成癌前病变,为胰腺管腺癌 (PDAC) 的发展提供了新的见解.
科学领域:
- 细胞生物学
- 癌症研究
- 胃肠病学
背景情况:
- 胰腺管腺癌 (PDAC) 是全球主要的癌症杀手.
- 胰腺细胞更新和PDAC启动的机制尚未完全理解.
- 癌症干细胞与许多癌症类型的瘤发展有关.
研究的目的:
- 确定负责胰腺更新和PDAC启动的细胞类型.
- 研究特定细胞亚群在胰腺瘤发生中的作用.
- 阐明参与PDAC早期发展的信号通路.
主要方法:
- 在小鼠模型中使用内源端粒酶逆转录酶 (Tert) 位点进行血统追踪.
- 在恒常状态和对瘤突变的反应中对细胞群的分析.
- 在切除的人类胰腺瘤中检测-ERK和KRAS突变.
主要成果:
- 发现了一种罕见的TERT阳性胰腺小细胞群 (TERThigh).
- 在恒常状态期间,高TERT细胞更新胰腺并形成扩张的克隆.
- 在TERT高细胞中突变Kras的表达加速克隆形成,并通过Ras-MAPK/ERK信号传递诱导转化为侵袭前病变.
- 人类胰腺瘤中常见的具有KRAS突变的细胞,表明早期的前体病变.
结论:
- 罕见的TERT高细胞是胰腺更新和PDAC启动的关键因素.
- 在TERT高细胞中维持KRAS突变驱动细胞扩张并启动瘤发生.
- 高TERT细胞代表胰腺癌的潜在细胞来源.
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