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在工程结直肠癌有机体中进行前期遗传查,确定转移的调节者
Xin Wang1, Zvi Cramer1, Nicolae Adrian Leu1
1Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104.
研究人员确定CTNNA1和BCL2L13是结直肠癌转移的关键抑制剂. 它们的丧失促进了癌细胞的扩散和生存,突出了转移性疾病的新治疗点.
科学领域:
- 在瘤学瘤学.
- 遗传学 遗传学是一种遗传学.
- 分子生物学分子生物学
背景情况:
- 转移性增长是一个复杂的过程,涉及多个步骤,从原发性瘤细胞脱落到远端部位扩散.
- 鉴定转移的遗传驱动因素是具有挑战性的,因为与早期瘤发生驱动因素相比,它们的潜在变异性具有挑战性.
研究的目的:
- 开发和应用一个查框架来识别转移调节者.
- 通过基因查在结直肠腺癌中发现新的转移特异性抑制剂.
主要方法:
- 在大肠直肠腺癌的基因定义器官模型中利用基于CRISPR/Cas9的查.
- 进行了体外查以检测入侵和迁移.
- 在一个同基因小鼠模型中进行了对转移的 орто托普体内查.
主要成果:
- 确定CTNNA1 (卡德林1) 和BCL2L13 (BCL2Like13) 作为转移特异性抑制剂.
- 证明CTNNA1的丧失可以增强细胞的入侵和迁移.
- 表明BCL2L13的丧失促进了 anchorage独立的生存,并改变了巨细胞的两极分化.
结论:
- CTNNA1和BCL2L13是新的调节剂,它们专门抑制转移而不会影响原发性瘤生长.
- 验证了瘤器官模型在体内大规模遗传查中的实用性.
- 建立了一个框架,用于识别具有潜在治疗影响的转移调节器.
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