佳能和核mTOR在依赖雄激素的前列腺癌细胞中指定了不同的转录程序
Yonghong Chen1,2, Lingwei Han1,2, Catherine Rosa Dufour1
1Goodman Cancer Institute, McGill University, Montréal, Québec, Canada.
核和细胞质mTOR (拉巴胺的机械性标) 信号通路控制前列腺癌中不同的基因程序. 这项研究揭示了核mTOR如何与雄激素受体和FOXA1相互作用以调节基因表达,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
- 细胞生物学 细胞生物学
背景情况:
- 猛素的哺乳动物标 (mTOR) 是细胞生长和新陈代谢的关键调节剂.
- mTOR通过转录因子酸化和直接染色体关联影响基因表达.
- 核mTOR (nmTOR) 整合了与染色体重塑剂,AR和FOXA1.1的雄激素信号传输.
研究的目的:
- 研究细胞质mTOR (cmTOR) 和nmTOR在前列腺癌中的不同作用.
- 阐明FOXA1在nmTOR介导的转录调节中的贡献.
- 探索针对前列腺癌mTOR信号的治疗机会.
主要方法:
- 具有特定mTOR定位信号 (核/细胞质) 的工程细胞.
- 在雄激素受体阳性前列腺癌细胞中进行了转录组概况 (RNA-seq).
- 进行了生物化学和全基因组转录组分析,包括囊细胞组概况.
主要成果:
- nmTOR可以降低素反应途径的一个子集,而不依赖酶活性.
- cmTOR以酶依赖的方式调节细胞周期基因特征.
- 在功能上,nmTOR与AR和FOXA1相互作用;FOXA1剥离重新编程nmTOR的目标.
结论:
- 在前列腺癌中,nmTOR和cmTOR调节了不同的基因程序.
- nmTOR,AR和FOXA1形成了一个控制特定基因程序的复合体.
- 准这些独特的mTOR通路为前列腺癌提供了新的治疗策略.
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