乳腺癌细胞中介细胞过渡和转移是由DAP5/eIF3d介导的选择性mRNA翻译指导的转移和转移
Amandine Alard1, Olga Katsara1, Tiffany Rios-Fuller1
1Department of Microbiology, NYU School of Medicine, New York, NY 10016, USA.
Cell reports
|June 14, 2023
概括
一个涉及DAP5/eIF3d的新型mRNA转化途径对于癌症转移和上皮转移至介质细胞转移 (EMT) 至关重要. 这一途径选择性地转化关键基因,为晚期癌症提供新的治疗点.
科学领域:
- 分子生物学分子生物学
- 癌症研究 癌症研究
- 翻译医学是一种翻译医学.
背景情况:
- 癌细胞的可塑性允许通过诸如上皮细胞转移到介质细胞转移 (EMT) 等过程的生存和转移.
- 标准上限依赖的mRNA翻译涉及eIF4E/mTORC1,但癌症中可能存在其他机制.
- 了解这些机制是针对癌症入侵和转移的关键.
研究的目的:
- 调查癌症进展中mRNA翻译的另类机制.
- 确定DAP5/eIF3d复合体在癌症转移,EMT和血管生成中的作用.
- 探索DAP5作为转移性乳腺癌的潜在治疗点.
主要方法:
- 进行了全基因组的转录组和转录组分析.
- 研究使用了人类和小鼠乳腺癌模型.
- 研究了DAP5/eIF3d在EMT,细胞迁移,入侵,转移和血管生成中的作用.
主要成果:
- DAP5/eIF3d复合体选择性地翻译编码EMT因子,迁移蛋白和血管生成调节者的mRNA.
- 在转移性乳腺癌中,DAP5过度表达,与无转移性生存率差相关.
- DAP5对于转移,EMT和血管生成至关重要,但在癌症模型中并非主要瘤生长.
结论:
- 癌细胞利用两个不同的mRNA翻译途径:eIF4E/mTORC1和DAP5/eIF3d.
- DAP5/eIF3d通路对于癌细胞的可塑性,入侵,转移和血管生成至关重要.
- 这些发现揭示了癌症进展期间显著的mRNA翻译可塑性,并突出了DAP5作为潜在的治疗点.
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