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Wnt的激活会扰乱细胞竞争,并通过NF-κB-MMP21通路引起转化细胞的扩散入侵
Kazuki Nakai1, Hancheng Lin1, Shotaro Yamano2
1Division of Cancer Biology, Research Institute for Biomedical Sciences, Tokyo University of Science, Noda, Chiba, 278-0022, Japan.
Nature communications
|November 4, 2023
概括
癌细胞利用细胞竞争,看起来不适合,导致反向淘汰和入侵. 阻止NF-κB信号传递恢复正常的细胞竞争,防止结直肠癌的进展.
科学领域:
- 细胞生物学 细胞生物学
- 癌症研究 癌症研究
- 分子瘤学分子瘤学
背景情况:
- 正常的上皮细胞通过细胞竞争消除了RasV12转化细胞.
- 危及细胞竞争和驱动致癌的因素尚未完全理解.
研究的目的:
- 调查序列基因突变如何影响RasV12诱导的细胞竞争在肠道上皮组织.
- 阐明细胞竞争受损和癌症发展背后的机制.
主要方法:
- 使用了RasV12转化肠上皮模型.
- 分析了模仿多序列致癌的基因突变.
- 评估细胞挤出方向性和侵入性.
- 研究了MMP21和NF-κB信号通路.
- 检查了人类结直肠癌样本.
主要成果:
- 通过Wnt激活的上皮质逆转了RasV12细胞挤出方向,通过MMP21上调导致基底分层.
- 上调的MMP21,部分由NF-κB信号传导介导,促进了侵袭性癌症的发展.
- 阻止NF-κB信号传递恢复了RasV12细胞的尖端消除.
- 在早期人类结直肠癌中,NF-κB-MMP21轴显著升高.
结论:
- 序列突变可以重新编程细胞竞争,有利于转变的细胞入侵.
- NF-κB-MMP21轴是RasV12诱导的致癌和结直肠癌中的关键途径.
- 准这一轴可能为预防癌症入侵提供治疗策略.
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