E2F1激活乳腺纤维细胞,并促进它们的膜前致癌作用
Layla A Al-Kharashi1,2, Falah H Al-Mohanna3, Abdelilah Aboussekhra4
1Department of Molecular Oncology, King Faisal Specialist Hospital and Research Center, Riyadh, 11211, Kingdom of Saudi Arabia.
Scientific reports
|February 5, 2025
概括
转录因子E2F1在乳腺癌中激活癌症相关纤维细胞 (CAF),促进瘤生长和耐药性. 针对CAF中的E2F1可能为乳腺癌患者提供新的精密治疗方法.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 乳腺癌 (BC) 是复杂的微环境,涉及瘤细胞,层细胞和细胞外基质.
- 与癌症相关的纤维细胞 (CAFs) 是通过膜信号传递,由转录因子调节的BC进展的关键参与者.
研究的目的:
- 研究转录因子E2F1在乳腺癌中CAFs激活和功能中的作用.
主要方法:
- 在CAF中对E2F1表达的比较分析与瘤对应纤维细胞 (TCF) 的比较分析.
- 纤维细胞中E2F1的宫外表达和敲除.
- 在体外和体内对纤维细胞诱导的表皮细胞转移到介质细胞 (EMT) 和乳腺癌细胞的干细胞的评估.
- 评估乳腺癌细胞对化疗 (cisplatin) 的敏感性,如果存在被操纵的纤维细胞.
主要成果:
- 在CAF中,E2F1水平高于TCF.
- 纤维细胞中的异位E2F1表达诱导了亲致癌的膜效应,增强了BC细胞中的EMT和干细胞.
- E2F1 knockdown使CAF正常化,并降低了它们的致癌活性.
- 纤维细胞中高水平的E2F1赋予了BC细胞的化学抵抗力,而E2F1缺乏增加了对西斯的敏感性.
结论:
- 转录因子E2F1对于激活乳腺层纤维细胞和驱动亲致癌效应至关重要.
- E2F1在乳腺癌的发展,进展和化学抵抗方面发挥着重要作用.
- E2F1代表了精准医学在乳腺癌治疗中的潜在治疗目标.
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