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从化疗后冲击中脱离分化瘤细胞的WNT条件机制
Irina A Tsydenova1,2, Daria S Dolgasheva1,2, Ksenia A Gaptulbarova1,2,3
1Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, 634028 Tomsk, Russia.
Cancers
|June 22, 2023
概括
拷贝数异常 (CNA) 激活WNT信号通路基因驱动化学疗法后分化瘤细胞的出现. 抑制WNT信号传递在乳腺癌模型中部分阻止了这种脱差过程.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症干细胞 癌症干细胞
背景情况:
- 化疗可以诱导差异化瘤细胞的休克状态,可能导致它们重新出现.
- 在这个过程中,特定的遗传变化的作用,如拷贝数异常 (CNAs),仍然不完全理解.
- WNT信号通路的激活与各种癌症和干细胞生物学有关.
研究的目的:
- 调查假设WNT信号通路基因拷贝数异常 (CNA) 激活驱动化学治疗后分化瘤细胞的出现.
- 探索向WNT信号的潜力,作为预防瘤细胞重新出现的治疗策略.
主要方法:
- 评估了多个乳腺癌细胞系中CNAs的遗传格局,以对WNT通路激活进行排名.
- 选择了T47D (WNT激活) 和BT-474 (WNT非激活) 细胞系进行进一步研究.
- 使用IL6诱导的脱差和在cisplatin和WNT抑制剂ICG-001.001的存在下形成的乳球.
主要成果:
- 与BT-474细胞不同的是,与WNT通路激活的T47D细胞在西斯普拉丁治疗后脱离分化并形成乳球.
- 在T47D细胞中,WNT抑制剂ICG-001完全抑制了脱差.
- ICG-001 部分降低了,但并没有消除两个细胞系的脱差能力.
结论:
- 这项研究支持了异位WNT信号通路基因激活对化疗后分化瘤细胞的出现负责的假设.
- 这些发现强调了WNT信号在瘤细胞存活和治疗后脱差中的关键作用.
- 准WNT信号提供了一个潜在的治疗途径,以克服化疗耐药性.
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