功能性基因组选揭示了FERMT2作为YAP/TAZ驱动瘤发生性的关键调节者
Arianna Chiesa1, Vittoria Poli1, Ottavio Croci1
1Center for Genomic Science of IIT, CGS@SEMM (Istituto Italiano di Tecnologia at the European School of Molecular Medicine), Fondazione Istituto Italiano di Tecnologia (IIT), Milan, Italy.
我们通过调节YAP/TAZ信号传递,确定FERMT2对乳腺癌细胞存活至关重要. 失去FERMT2会影响瘤生长,这表明它是高YAP/TAZ活性癌症的潜在治疗标.
科学领域:
- 细胞生物学 细胞生物学
- 分子瘤学分子瘤学
- 癌症信号传递 癌症信号传递
背景情况:
- 酵母和TAZ (Yes相关蛋白和Tafazzin) 是机械转导,发育和组织平衡的关键调节者.
- YAP/TAZ信号的失调与各种疾病有关,尤其是癌症.
- 识别YAP/TAZ的上游调节者对于理解和准癌症进展至关重要.
研究的目的:
- 确定乳腺癌细胞适应性中YAP/TAZ信号传递的基本调节者.
- 阐明FERMT2在YAP/TAZ通路激活和乳腺癌瘤性中的作用.
主要方法:
- 使用定制的sgRNA库进行CRISPR/Cas9功能丧失遗传查 (体外和体内).
- 大规模癌症数据集的生物信息分析.
- 通过FERMT2淘汰/沉默,YAP/TAZ目标基因表达分析和西式涂抹的功能验证.
主要成果:
- FERMT2被确定为一个关键的YAP/TAZ调节器,对乳腺癌细胞适应性和瘤性至关重要.
- 在三阴性乳腺癌细胞中,FERMT2的丧失影响了YAP/TAZ核积累,基因表达和扩散.
- FERMT2通过整合素介导的FAK激活来调节YAP/TAZ,独立于Hippo通路.
结论:
- FERMT2是通过FAK传输YAP/TAZ信号的关键上游调节器.
- YAP/TAZ是整合素活性的主要影响者.
- 在具有高YAP/TAZ信号的癌症中,FERMT2代表了潜在的治疗脆弱性.
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