默特基驱动三阴性乳腺癌的扩散和转移潜力
Mari Iida1, Bridget E Crossman1, Kourtney L Kostecki1
1Department of Human Oncology, University of Wisconsin-Madison, Madison, WI 53705, USA.
International journal of molecular sciences
|May 25, 2024
概括
默特基受体氨酸激酶驱动三阴性乳腺癌 (TNBC) 的生长和转移,部分是通过增加内分泌素 (ENG) 表达. 同时准MerTK和ENG可能为TNBC提供新的治疗策略.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 由于缺少雌激素受体,孕受体和HER2表达,三阴性乳腺癌 (TNBC) 缺乏向疗法.
- 了解TNBC分子驱动因素对于开发新型组合疗法至关重要.
- 在TNBC增殖和转移中MerTK受体氨酸激酶的作用需要进一步研究.
研究的目的:
- 评估MerTK在TNBC扩散和入侵/转移潜力的作用.
- 研究由TNBC中MerTK调节的下游信号通路和分子效应器.
- 为了确定内分泌蛋白 (ENG) 是否在TNBC中调解MerTK的转移前效应.
主要方法:
- 免疫组织化学评估患者衍生的TNBC异种移植中的MerTK表达.
- 在人类TNBC细胞系中稳定过度表达MerTK (SUM102).
- 纳米链 nCounter 分析和蛋白质组定型,以确定 MerTK 调节的通路和蛋白质.
- 通过CRISPR-Cas9技术,在MERTK过度表达的TNBC细胞中消除内分泌蛋白 (ENG).
主要成果:
- 在58%的TNBC异种移植中表达了MerTK.
- 过度表达MerTK增加了TNBC细胞的增殖,体内瘤的生长,迁移,入侵和肺转移.
- 梅特基信号上调的通路促进细胞周期的进展和存活,并增加内分泌蛋白 (ENG) 产量.
- 在MERTK过度表达细胞中,ENG淘汰显著减少了肺转移 (~4倍),同时保持了瘤生长.
结论:
- 默特基促进了TNBC的增殖和转移,部分是通过对内分泌蛋白 (ENG) 的上调调节.
- 在TNBC中,MerTK监管了一个独特的扩散签名.
- 同时准MerTK和ENG为TNBC提供了一个潜在的新疗法策略.
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